Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Redesigned Surface Manager – Control complex visualizations effortlessly with a modern, persistent interface that allows for real-time, non-modal editing of surface styles, colors, and transparency
• Persistent measurements – Geometric measurements now persist with the entries, allowing for uninterrupted structural comparison across multiple conformers and states
• Standalone density map import – Accelerate Cryo-EM and crystallography workflows with direct, standalone density map import
• Maestro Assistant modes (open beta) – A context-aware AI partner that intelligently toggles between ‘Ask’, ‘Execute’, and ‘Auto’ modes to seamlessly bridge documentation and direct action

Binding Site & Structure Analysis

Mixed Solvent MD (MxMD)

• Added support to command line MxMD driver to seamlessly execute all simulations and compile results from combined MxMD/SiteMap cryptic pocket identification workflow

WaterMap

• WaterMap now supports use of the OPLS_2005 forcefield and TIP4P water model

Hit Identification & Virtual Screening

Docking

• Understand, optimize, and troubleshoot native redocking experiments with new Docking Report to maximize docking performance

Lead Optimization

FEP+

• GraphDB/Web services can optionally download only the primary FMP file and not the FMPdb reducing time to analyzing results
• FEP+ workflows now support execution on cost-effective preemptible nodes
• Use 2D Sketcher to define Core SMARTS for FEP+
• Improved handling of categorical assay data in FEP+ statistical analysis

FEP+ Protocol Builder

• Sample three levels of salt concentrations in protocol optimization
• Sample automatic membrane placement in protocol optimization

FEP+ Pose Builder

• Automatically create accurate and clash-aware FEP-ready poses with FEP+ Pose Builder: Generate high-quality ligand alignments faster to run FEP+ at scale with an automated workflow designed for unbiased selection and robust atom-mapping
• LiveDesign FEP+ Pose Builder protocol now supports generating FMP files for cycle-closure FEP calculations

Quantum Mechanics

• Employ xTB and MLFFs including QRNN, MPNICE, and UMA in AutoTS from command line for shorter calculation times
• Faster batch calculations by optimized CPU core assignments for all multithreaded Jaguar batch calculations

Spectroscopy

• New corrections for C-Br and C-I bonds in 13C NMR spectra

De Novo Design

AutoDesigner – R-group Design

• Explore large chemical spaces to identify optimal R-groups with new AutoDesigner R-group Design Panel now accessible by setting a feature flag
• Added optional QED score (Quantitative Estimate of Drug-Likeness) for AutoDesigner R-group Design ideas

AutoDesigner – Core Design

• Explore large chemical spaces to identify optimal core replacements with new AutoDesigner Core Design Panel now accessible by setting a feature flag
• Added optional QED score (Quantitative Estimate of Drug-Likeness) for AutoDesigner Core Design ideas

Education Content

• Introducing a new, more interactive tutorial experience, letting users intuitively click through the steps of a workflow right in the tutorial. This approach is being piloted in two tutorials.
  • Updated Tutorial: Structure-Based Virtual Screening Using Glide
  • Updated Tutorial: Introduction to Structure Preparation and Visualization
• Fully re-worked learning content on Antibody Modeling:
  The “Antibody Visualization and Modeling in BioLuminate” tutorial has been replaced by a new suite of tutorials organized in a learning path together with other helpful resources.
  • New Learning Path: Antibody Modeling
  • New Tutorial: Antibody Structure Prediction and Visualization with BioLuminate
  • New Tutorial: Humanizing Antibody Structures with BioLuminate
  • New Tutorial: Antibody – Antigen Docking with PIPER
  • New Tutorial: Improving Antibody Stability/Affinity Using MM-GBSA Residue Scanning
• New Tutorial: Generating ternary complex structures to enable rational design of targeted protein degraders
• Updated Tutorial: BACE1 Inhibitor Design Using Free Energy Perturbation
• New Quick Reference Sheet: Force Field Builder
• New Quick Reference Sheet: Ligand Interaction Diagram

Biologics Drug Discovery

• Release of MacroMolecular Pose Filter – Select the most plausible or relevant structural models of a macromolecular complex from a larger set of generated possibilities
• New protein descriptor – ASPmax – Added ASPmax (Maximum Average Surface Property) to our descriptor set. Used to predict the retention time of proteins in hydrophobic interaction chromatography (HIC) columns and aggregation risk
• Search and filter non-standard residues – Support for text-based searching and filtering of non-standard residues based on labels in the Name, Code, and Description columns
• Residue Lookup in the MMGBSA residue scanning panel – Quickly search and find residues to mutate
• Classification of residue scanning results – Color codes residue scanning results to designate positive, neutral or negative mutational variants based on energy score cut-offs

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Defect Formation Energy: Workflow solution to analyze point defects in crystals
• Options to set frequency cutoff / harmonic threshold in the Phonon DOS Viewer
• Support for TB09 density functional (command line)
• Support for rVV10-SCAN density functional (command line)
• Support for NpT ensemble in QE BOMD simulations (command line)
• (+MATSCI_NEB_MLFF) MLFF integration in NEB

MS Surface

Product: MS SurfChem

• Desorption Enumeration: WAM to open results in Adsorption Energy

Microkinetics

Product: MS Microkinetics

• Option to view selectivities and degrees of selectivity control
• Option to load/save archived MKM output
• Option to export reaction view as an image (PNG) file
• Results from individual stages made visible from the analysis panel

Optoelectronics Genetic Optimization

Product: Genetic Optimization (GA)

• Support for setting target property based on models from ML Property Prediction

Active Learning Optoelectronics

Product: Active Learning Optoelectronics

• Option to set target values excluded from optimizations

Reactivity

Product: MS Reactivity

• Nanoreactor: Option to specify separate hosts for driver and subjobs
• Nanoreactor: (+NANOREACTOR_AUTOTS) Automatic transition state search for elementary reaction network calculations via AutoTS
• Nanoreactor: Option to skip generating trajectory files
• Nanoreactor: User control over the time interval between trajectory frames
• Reaction Network Profiler: Option to refine conformer geometries using UMA (MLFF)
• Reaction Network Profiler: Option to assign stoichiometric multipliers for reactants

Transport Calculations via MD simulations

Product: MS Transport

• Ionic Conductivity: Support for MLFF

Dielectric properties

Product: MS Dielectric

• Complex Permittivity: Support for multi-component systems

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• CG FF Builder: Improved detection and mapping of non-isomorphic residues
• CG FF Builder: Automated particle naming scheme with chemical context
• CG FF Assignment: Up to 15x speed-up for models with a large number of particle types
• Coarse-Grained Mapping: Residue number and name retained through mapping
• Coarse-Grained Mapping: Option to import SMARTS patterns from previous use
• Speed-up for DPD simulations of up to 30% with improved cutoff margins

Complex Bilayer Builder

Product: MS Complex Bilayer Builder

• Complex Bilayer: (+COMPLEX_BILAYER_BUILDER_EXTENDED_LIPID_LIB) Expanded list of default lipids
• Complex Bilayer: Increased limit for water padding depth to 5000 Å
• Complex Bilayer: Support for custom-trained OPLS
• Membrane Analysis: (+MEMBRANE_ANALYSIS_PREP_FOR_FEP) Support for generating poseviewer formatted files compatible with FEP calculations
• Membrane Analysis: Support for applying multiple leaflet-finding algorithms

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Improved panel interface for model selection
• MD Descriptors: User control over simulation system size (max # of atoms)
• MD Descriptors: Support for formulation input with path assigned to structure files
• MLFF Calculations: Option to set constraints to atomic positions
• MLFF Calculations: Support for running on GPU nodes

Formulation ML

Product: MS Formulation ML

• Formulation ML: ‘Learned Fingerprint’ as a new option to feature space
• Formulation ML: Advanced option to process (‘impute’) training set data with partially missing descriptors
• Formulation ML: Improved UI for parity plot
• Formulation ML: Support for building machine learning models using training datasets with missing chemical (SMILES) information
• Formulation ML: Target property displayed in the ‘Performance’ tab
• Formulation ML: User control over correlation threshold between features
• Formulation ML Optimization: Support for custom-ingredient descriptors
• Formulation ML Optimization: Support for multi-CPU parallelization
• Formulation ML Optimization: Option to use genetic algorithms for formulation optimization

Layered Device ML

Product: MS Layered Device ML

• OLED Device ML: User control over correlation threshold between features
• OLED Device ML: Target property displayed in the ‘Performance’ tab

MS Maestro Builders and Tools

• Adsorption Enumeration: WAM to open results in Adsorption Site Finder / Adsorption Energy
• Adsorption Site Finder: WAM to open results in Adsorption Energy
• Adsorption Enumeration: Improved organization of output structures in the Project Table
• Adsorption Site Finder: Up to 200x of speed-up for jobs using MLFF
• Clean Up Structures: Support for MLFF
• Disordered System: Option to define residue name for components
• Support for converting *.vis files to *.cub formatted files (command line)
• Polymer: Import of coupling probabilities from a CSV formatted file
• Polysaccharide: (+POLYSACCHARIDE_BUILDER) Simplified model building solution for linear-chain polysaccharides
• Single Complex: Updated list of bridging ligands
• Query Bonds: Display of polyhedra for molecular crystals
• Query Bonds: Search for and modification of non-bonded atom pairs

Classical Mechanics

• Droplet: Support for using pre-assembled droplet models
• Droplet: Support for computing contact angles with hydrate surfaces
• Elastic Constants: Support for MLFF
• (+ALLOW_OLD_FORCEFIELD_PARAMETERS) Support for running MD using OPLS4/OPLS5 parameters with backwards compatibility (2025-4 and older)
• MD Multistage: FF type for the input structure displayed in the panel
• Stress Strain: Support for MLFF
• Stress Strain: Option to use velocities from previous strain steps
• Surface Tension: Improved analysis with block averaging scheme
• Tg: (+THERMOPHYSICAL_PROPERTIES_MLFF) Support for MLFF
• Umbrella Sampling: Workflow solution to run umbrella sampling algorithm for small molecules near lipid and surfactant bilayers
• Umbrella Sampling: Displaying quantity of overlap between windows
• Viscosity: Adjusted default timestep (0.5 fs) for MLFF simulations

Quantum Mechanics

• Adsorption Energy: Option to pre-optimize structures with MLFF
• Adsorption Energy: Support for atomic positional constraints with MLFF
• Crest: (+MATSCI_CREST_QCG) CREST Quantum Cluster Growth Utility
• QM Multistage: Option to select GFN2-xTB from the list of theory
• Optoelectronic Film Properties: Display of refractive index ratio per molecular species
• Reaction Network Viewer: Comprehensive analysis viewer GUI for viewing networks created by Reaction Network Profiler and Nanoreactor

Education Content

• New Tutorial: Catalytic Selectivity Through Microkinetic Modeling
• Updated Tutorial: Defect Formation Energy Calculation
• Updated Tutorial: Nanoreactor
• Quick Reference Sheet: Clean Up Structures

Education Content

Life Science

• Introducing a new, more interactive tutorial experience, letting users intuitively click through the steps of a workflow right in the tutorial. This approach is being piloted in two tutorials.
  • Updated Tutorial: Structure-Based Virtual Screening Using Glide
  • Updated Tutorial: Introduction to Structure Preparation and Visualization
• Fully re-worked learning content on Antibody Modeling:
  The “Antibody Visualization and Modeling in BioLuminate” tutorial has been replaced by a new suite of tutorials organized in a learning path together with other helpful resources.
  • New Learning Path: Antibody Modeling
  • New Tutorial: Antibody Structure Prediction and Visualization with BioLuminate
  • New Tutorial: Humanizing Antibody Structures with BioLuminate
  • New Tutorial: Antibody – Antigen Docking with PIPER
  • New Tutorial: Improving Antibody Stability/Affinity Using MM-GBSA Residue Scanning
• New Tutorial: Generating ternary complex structures to enable rational design of targeted protein degraders
• Updated Tutorial: BACE1 Inhibitor Design Using Free Energy Perturbation
• New Quick Reference Sheet: Force Field Builder
• New Quick Reference Sheet: Ligand Interaction Diagram

Materials Science

• New Tutorial: Catalytic Selectivity Through Microkinetic Modeling
• Updated Tutorial: Defect Formation Energy Calculation
• Updated Tutorial: Nanoreactor
• Quick Reference Sheet: Clean Up Structures

LiveDesign

What’s New in 2026-1

• Biologics
  • Design new biologics with point mutations using natural monomers
  • Upload custom monomers via API access, and view the monomers in the sequence viewer
  • Search for a subsequence within an annotated region of a Biologics entity, by selecting the annotation and numbering scheme from pre-filled dropdowns
  • Users can now color residues by property in the sequence viewer with any model that outputs the per-residue property/properties and color scheme mapping(optional) in the specified format, or with any Freeform column that contains the output
  • The “Biologics” and “Generic Entity” options in the “Type” dropdown menu of the Advanced search panel, have been unified to “Biologics/Others”
  • View branched and cyclic peptides in the sequence viewer
• LiveDesign AI Assistant: interact with LiveDesign using an AI assistant to create Freeform and Formula columns, create and update coloring rules, perform data analyses and plot data within the Assistant, and instantly find help documentation. Note that this capability requires the LiveDesign ML plugin
• Project Dashboards
  • View a project activity stream of newly added assay data and comments using the new “Activity” section
  • Entity count statistics and recently added entities shown in the Project Dashboard will now include all entities that are searchable to the project (e.g., compounds imported to unrestricted projects), instead of entities specifically imported to the project
• Models: Column as parameter models that use a 3D column as input now have access to the favorited pose, and the pose order that is represented in the LiveReport
• UX Improvements
  • Filter out un-run, failed, and pending model cells from your LiveReport
  • Drag a compound structure from the main spreadsheet directly to the Design, Search,or Advanced search panels without opening the panel first
  • Close LiveReport tabs by clicking on them with a middle mouse button click
  • 3D Visualizer: apply Stereolabels, Element label, and Atom Number labels to the selected atoms/residues/Chains

What’s Been Fixed

• Formulas that used the Lot Registration Date column as input would fail to calculate, and cause a red error bar to appear on the LiveReport. Those formulas now calculate correctly and do not cause an error
• Icons within the main spreadsheet cells to view a pose in the 3D visualizer, or in Maestro, would disappear when the cell was resized, and now remain visible
• Adding a click-to-run model column to a matrix widget would cause the widget to crash and not show data, and now click-to-run models appear correctly in the matrix widget
• Formulas using if() statements would fail to calculate when the if() statement used experimental assay cells that contained multiple values, in which one of those values was Null. Those formulas now calculate correctly
• The “Creating New Layout” dialog did not show an option to copy an existing layout, and now correctly shows that option.
• Editing a LiveReport’s title using the “Edit LiveReport Dialog” would result in moving the LiveReport to the Project Home folder, and now editing a LiveReport with that dialog will not move the LiveReport to a different folder
• Formatting option buttons on the Configure Matrix Widget dialog overlapped, which prevented accessing some formatting options, and now the buttons do not overlap
• Experimental assay data would show dashed lines underneath experimental values within the spreadsheet cells, and now do not show dashed lines
• The aggregateMax() and aggregateMin() formula functions now work for date columns
• Multi-chain or branched peptides are now accurately identified with incremental peptide numbers in their identifiers in sequence viewer.
• The sequence viewer now shows a message when TCRs with unsupported numbering schemes are used, and suggests to move to a supported numbering scheme for TCRs in the sequence viewer.
• When 3D visualizer is drilling down from the sequence viewer, selecting another entity in the sequence viewer does not reset the existing residue selection in the sequence viewer and 3D visualizer
• Parameterized models that used another model’s image columns as input would not calculate results, and now correctly calculate
• Recalculating a deleted model return would result in a permanently flashing cell, and now the cell will correctly show a Failed message
• When models returned a 3D output of type “other”, that 3D output was not accessible to other parameterized models, and now is accessible
• LDClient: the method get_models_by_name now includes an option to ignore archived models

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• One-click deletion of empty project table columns: A single menu action instantly removes all empty property columns from the entire Project Table, decluttering the workspace to allow a clearer focus on relevant data.
• “Select Entries in Table” from workspace right-click menu: Right-clicking any atom in the Workspace instantly locates and selects its corresponding entry in the Project Table, eliminating the need for manual searching in large projects.
• Maestro Assistant (Beta) enhancements: Maestro Assistant is now more interactive with the addition of a command history, copy-to-clipboard functionality, clearer mode notifications, and a streamlined feedback system.

Binding Site & Structure Analysis

SiteMap

• SiteMap now evaluates more sites than requested, returning the requested number of top-scoring sites by SiteScore

Desmond Molecular Dynamics

• Energy Decomposition Analysis panel now supports trajectories generated using custom force field parameters

Mixed Solvent MD (MxMD)

• Addition of immiscible probes in Mixed Solvent MD to better identify cryptic pockets: Use hydrophobic probes to stabilize transiently exposed pockets in an open conformation to increase their residence time and facilitate cryptic binding site identification

Ligand Preparation

Pharmacophore Modeling

• Use 1D similarities to screen against massive virtual spaces defined combinatorically with the combinatorial_explorer workflow (command line only)

Lead Optimization

Ligand alignment

• Non macrocycle alignment jobs can run as interactive tasks without submitting a job

Enumeration

• Return only Pathfinder retrosynthetic routes that include purchasable starting materials

FEP+

• Added ligand atomic RMSF analysis for RE-FEP calculations

FEP Protocol Builder

• Enable separate solvent and complex hot atom rules including None
• Enable sampling between OPLS4 and OPLS5 with the new Force Field version parameter

Quantum Mechanics

• Predict optical rotation as a function of wavelength
• Added support for 18 new double hybrid functionals
• Faster simulations with optimized CPU assignments for unbalanced batch jobs and workflows
• Employ QRNN, MPNICE and UMA MLFFs from Jaguar interfaces

Medical Chemistry Design

Ligand Designer

• Interactive Core Hopping: A new Core Swap workflow supports non-ring cores and enables true core hopping transformations, allowing for the exploration of diverse chemical space directly within an interactive design environment.
• Manual attachment point selection for macrocyclization: The newly renamed Macrocyclization workflow allows for the interactive selection of attachment points, providing precise chemical control that focuses linker enumeration on synthetically relevant designs.

De Novo Design

• New PDF report for AutoDesigner workflows to record input settings and summarize enumeration and filtering results

Drug Formulations

Crystal Structure Prediction

• Expansion of drug formulations applicability with highly accurate Z’=2 polymorph predictions (Beta): Identify stable crystal polymorphs with updated crystal structure prediction capabilities to sample, search and rank confidently

Alternative Modalities

Bifunctional Degraders

• Optionally build linkers between the two warheads in both directions when using the “Linkers only” option in the Generate Degrader Ternary Complexes interface
• Prioritize ternary complexes for linker design with a new interface to score degrader ternary complexes powered by a validated Metadynamics-based workflow (beta)

Education Content

• New Learning Path: T Cell Receptor Engineering
• New Tutorial: Enzyme Engineering with BioLuminate
• Updated Tutorial: Validating a Protein Free Energy Perturbation Model for Thermostability Predictions for Single Point Mutations (previously “Obtaining Protein Free Energy Perturbation Thermostability Predictions for Single Point Mutations”)
• Updated Tutorial: Improving the Thermostability of T4 Lysozyme Using Protein FEP+ Guided Design (previously “Introduction to Protein Thermostability Prediction using Protein FEP+”)
• Updated Tutorial: Ligand Binding Pose Generation for FEP+ (previously Ligand Binding Pose Prediction for FEP+ using Core-Constrained Docking)
• Updated Tutorial: Structure-Based Virtual Screening using Glide

Biologics Drug Discovery

• Predict T-Cell Receptor structures using TCRBuilder2 through Maestro (full release)
• Improved ability to visualize sequences before and after CDR grafting in Antibody Humanization Panel by replacing the pop-up sequence viewer with the MSV
• Streamlined visualization and plotting of mutation results by updating the mutations chart in the residue scanning results viewer interface
• Simpler analysis in the Residue Scanning Viewer by synchronization between chart and table
• In MM-GBSA Residue Scanning Viewer interface choose properties to plot on both axis, eg. plot affinity on x and stability on y-axis
• Easier setup of MM-GBSA Residue Scanning calculations through synchronization of selection between workspace and table, automatic fit-on selection, and ability to toggle visibility of select columns in property table
• New ASPmax protein descriptor capturing the maximum average surface property for aggregation propensity prediction (command line)

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• (+DEFECT_FORMATION_ENERGY) Defect Correction: Workflow solution to compute the defect formation energy
• Upgrade to Quantum ESPRESSO 7.5
• Support for 3-body dispersion correction
• Visualization of d-band center
• Support for finite displacement phonon calculations
• Reduced disk space usage for phonon calculations
• Option to set self-consistency threshold for phonons

MS Surface

Product: MS SurfChem

• Desorption Enumeration: Active entry shown in the workspace
• Desorption Enumeration: Support for enumerating associate desorption products

Microkinetics

Product: MS Microkinetics

• Option to calculate the degree of selectivity control
• Option to plot degree of rate control per species
• Option to set pressure schedule per species
• Setup for transition state lateness parameter to define lateral interactions
• Setup for adsorbate-adsorbate interactions via lateral scaling parameter
• Support for saving and loading reaction network files
• Support for simplified reaction entry using plain text
• Support for loading a microkinetic model from a workspace entry
• Support for plotting x-axis in log scale from the viewer panel
• User control over absolute and relative error tolerances
• Number of unphysical MKM steps displayed in viewer panel

Reactivity

Product: MS Reactivity

• Nanoreactor: Option to set spin for the final state of elementary reactions
• Nanoreactor: Refined setup for metadynamics cavity radius scaled from 0.1 to 1.0
• Nanoreactor: Product chemistry filtered by refined DFT or MLFF
• Nanoreactor: Reactant energy marked in the elementary reaction network mode
• Nanoreactor: Support for MLFF (UMA) energy refinement for open shell systems
• Reaction Network Profiler: Option to sort conformers from refined energy

Advanced Force Field Applications

Product: MS FF Applications

• Expanded support for MLFF selections in QM- and MD-based workflow solutions
• UMA (developed by Meta Platforms Inc.) added as MLFF option in QM-based workflows
• (+ENABLE_GRPC_MLFF_DESMOND) UMA (developed by Meta Platforms Inc.) added as MLFF option in MD-based workflows

Transport Calculations via MD simulations

Product: MS Transport

• Ionic Conductivity: Workflow solution to predict ionic conductivity in liquid electrolyte systems
• Viscosity: Option to turn off the SHAKE algorithm (command line)
• Viscosity: Support for MLFF

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Coarse-grained Mapping: Consistent, reusable names for sugar particles
• Coarse-grained Mapping: Improved restraint visualization
• Coarse-grained Mapping: MARTINI mapping of proteins
• Coarse-grained Mapping: MARTINI mapping of monosaccharides
• Coarse-grained Mapping: MARTINI mapping of cholesterol
• Coarse-grained Mapping: All-atom CMS created as input for CG FF Builder
• Coarse-Grained Mapping: Enhanced precision for SMARTS patterns to improve mapping and force field parameter reusability
• Coarse-Grained Mapping: Improved UX for the reuse of existing particle types
• Coarse-Grained Mapping: Visualization of the mapped system in the workspace
• Coarse-Grained Mapping: Use of antifreeze water molecules set by default
• CG FF Builder: NpT set as the default ensemble for MARTINI simulations
• CG FF Builder: Option to keep proteins rigid during the model building stage
• CG FF Builder: Option to set the masses to standard MARTINI particle types
• CG FF Builder: Mapping of a small ion-water cluster to a single MARTINI particle
• CG FF Builder: Support for the reuse of CG particle types with identical names
• CG FF Builder: Support for loading CG mapping output as input

Complex Bilayer Builder

Product: MS Complex Bilayer Builder

• Complex Bilayer: Model building solution for complex / multi-component bilayers of molecular materials including protein-based membranes
• Membrane Analysis: Workflow solution to analyze membrane structural features

Formulation ML

Product: MS Formulation ML

• Formulation ML: Support for parallel training and predictions of multiple models
• Formulation ML Optimization: Improved UX for loading models
• Formulation ML Optimization: Option to select random optimization for models
• Formulation ML Optimization: Option to stop optimization prior to convergence
• Formulation ML Optimization: Option for cost optimization
• Formulation ML Optimization: Support for composition constraints with Bayesian optimization
• ML Model Manager: Option to export and update descriptors for ingredients
• ML Model Manager: Automatic selection for the newly loaded model
• ML Model Manager: Access for model names to be edited by user
• ML Model Manager: Option to estimate MPO scores on model predictions

Layered Device ML

Product: MS Layered Device ML

• OLED Device ML: Advanced options for model training
• OLED Device ML: Option to export the training set data
• OLED Device ML: Support for parallel training and predictions of multiple models
• OLED Device ML: Option to use molecular model predictions as descriptors

MS Maestro User Interface

• Maestro: Job Monitor to display the cause of failures for failed jobs
• Maestro: Ribbon style enabled in the workspace for protein representations

MS Maestro Builders and Tools

• Complex Builder: Option to turn on/off IUPAC name assignment for ligands
• Complex Builder: Support for building dimers with an atom bridging two metals
• Disordered System: Preservation of protein residue information by default
• Disordered System: Option to set the system size by the total number of atoms
• Materials Science Panel Explorer: GUI to search and list panels by the application, method, chemistry, and product of interest
• Meta Workflows: Matched settings for the Brownie stage with the MD Multistage
• Optoelectronic Device Designer: Option to import materials data from a file
• Optoelectronic Device Designer: Option to export materials and device data
• Optoelectronic Device Designer: Option to remove materials from the database
• Optoelectronic Device Designer: Plot for numerical energy levels
• Optoelectronic Device Designer: Plot for numerical layer thicknesses
• Solvate System: Option to specify particle radii for coarse-grained models
• Solvate System, Structured Liquid GUI: (+MATSCI_PACKMOL_PBC) Periodic boundary conditions retained when building structures

Classical Mechanics

• Cluster Analysis: (+CLUSTER_DENSITY_PROFILE) Radial density profile for clusters
• Evaporation: Support for MLFF
• Evaporation: Setup for evaporation zone in radial distance from center of mass
• Polymer Crosslink: (+POLYMER_CROSSLINK_MODES) Option to select fast crosslinking mode
• Thin Plane Shear: Support for MLFF
• Thin Plane Shear: Option to use custom MLFF
• Umbrella Sampling: User control over potential of mean force (PMF) calculations
• Umbrella Sampling: Visualization of probability distribution overlap matrix
• Visualize Restraints: Visualization of multiple restraints

Quantum Mechanics

• Adsorption Site Finder: Support for MLFF
• Bond and Ligand Dissociation: Support for MLFF
• QM Multistage: Support for MLFF selection on the Theory tab
• Optoelectronic Film Properties: Advanced transition dipole moment analysis with distributions over angle, distance, and depth
• Probe Grid Scan: VdW radius used as atomic radius for metal atoms
• Probe Grid Scan: Support for scanning open shell systems using MLFF (UMA)

Education Content

• New Tutorial: Simulating Complex Protein Solutions
• New Tutorial: Creating a Coarse-Grained Model for Protein Formulations
• New Tutorial: Building and Analyzing a Complex Lipid Bilayer and Embedding a Membrane Protein
• New Tutorial: Ionic Conductivity
• New Tutorial: Optimizing Viscosity and Cost in Formulations with Missing Structural Data
• New Tutorial: Locating Adsorption Sites on Surfaces
• Updated Tutorial: Atomic Layer Deposition
• Updated Tutorial: Microkinetic Modeling
• Quick Reference Sheet: Materials Science Panel Explorer

Education Content

Life Science

• New Learning Path: T Cell Receptor Engineering
• New Tutorial: Enzyme Engineering with BioLuminate
• Updated Tutorial: Validating a Protein Free Energy Perturbation Model for Thermostability Predictions for Single Point Mutations (previously “Obtaining Protein Free Energy Perturbation Thermostability Predictions for Single Point Mutations”)
• Updated Tutorial: Improving the Thermostability of T4 Lysozyme Using Protein FEP+ Guided Design (previously “Introduction to Protein Thermostability Prediction using Protein FEP+”)
• Updated Tutorial: Ligand Binding Pose Generation for FEP+ (previously Ligand Binding Pose Prediction for FEP+ using Core-Constrained Docking)
• Updated Tutorial: Structure-Based Virtual Screening using Glide

Materials Science

• New Tutorial: Simulating Complex Protein Solutions
• New Tutorial: Creating a Coarse-Grained Model for Protein Formulations
• New Tutorial: Building and Analyzing a Complex Lipid Bilayer and Embedding a Membrane Protein
• New Tutorial: Ionic Conductivity
• New Tutorial: Optimizing Viscosity and Cost in Formulations with Missing Structural Data
• New Tutorial: Locating Adsorption Sites on Surfaces
• Updated Tutorial: Atomic Layer Deposition
• Updated Tutorial: Microkinetic Modeling
• Quick Reference Sheet: Materials Science Panel Explorer

LiveDesign

What’s New in 2025-4

• Form Templates: Save a Form as a template, and add the Form to an existing LiveReport. Manage Form templates in the Project Dashboard, and add them to a LiveReports.
• Freeform column audit trail: Track changes to Freeform columns, and hover over a clock icon to see a reverse chronological history of all edits, including the username, date, and time
• Search
  • Create query groups for grouping query conditions in the Advanced search panel, and select if a certain query group will be based on Parent or Child properties (by selecting “Match by property” or “Match by Child” option for the group)
  • The “Biologics” and “Generic Entity” options in the “Type” dropdown menu of the Advanced search panel, have been unified to “Biologics/Others”
  • View the result count for sequence-based searches on the Search panel, similar to what is displayed for structure-based searches.
  • The following quick add options (that appear when user clicks “Add query” in the Advanced search panel have been moved to the top of the Search panel:
    • All IDs
    • Compound Structure
    • Subsequence
    • Project
    • Database/Dataset
    • Presence in LiveReport
    • Query Group
• Updated formula dialog:
  • Larger formula expression editor
  • Search for columns and functions
  • Quickly select commonly used functions
  • Spot missing closing parentheses through color-matched parentheses to ensure formula accuracy
• Entity Grouping Relationship Manager:
  • Use the LiveReport as an Entity Bank: Directly use a LiveReport to leverage existing search and filter functionalities
  • Metadata Columns: Add columns to specify relationship information, like subcomponent count
  • Visualize Entity Type: The relationship table now shows entity types to ensure you select the right subcomponents
  • Modernized UI: A complete UI overhaul makes the tool more intuitive and user-friendly
• LDClient: A new method called “live_reports_compounds_search” has been introduced, that retrieves all LiveReports containing the supplied list of Corporate IDs
• 3D Visualizer: The order of the ligands docked poses listed in 3D visualizer are the same as the order of results listed in the model output cell in the spreadsheet

What’s Been Fixed

• Formulas:
  • Formulas would occasionally show blank cells and require a LiveReport refresh to show values, and now show values immediately
  • Formulas that used model inputs, which had multiple values in the input model cell, would occasionally cause red error bars to appear on the LiveReport, and now correctly calculate.
  • Formulas that output a single string would not wrap text values, and now wrap text values in the LiveReport cell
  • Formulas that used an if() function to detect the presence of a string value would fail to calculate if the input was a string column. For example if([string_column],”true”,”false”) would fail. These formulas now successfully calculate
• Sketcher:
  • Hovering the mouse cursor over the sketcher would not permit pasting in the sketcher, and now hovering over the sketcher changes the browser’s focus to the sketcher so that pasting is allowed
• Search:
  • LiveReports in row-per-experiment mode would not rerun auto-updating advanced searches after 24 hours, and now correctly run auto-updating advanced searches
• Spreadsheet:
  • Repeatedly copying cells from the LiveReport would fail in Firefox, and now correctly copy the cell contents
  • Click-to-run models would show a “3D not available” message in cells immediately after clicking the Run button, and now correctly show the pending cell icon
  • Users who were not permitted to change a Freeform column’s value could drag Kanban tiles to change the Freeform column value, and error messages would appear. Users can no longer drag these tiles
  • The LiveReport picker dialog would appear blank until it was resized, and now shows LiveReports immediately
• Sequence viewer:
  • Data on child entities would not appear in the sequence viewer, and now correctly appears
• Ligand Designer:
  • Growth space calculation for a ligand with <5 heavy atoms should now fail saying ‘Could not create growth space. Too few heavy atoms in the ligand’.
• 3D Visualizer:
  • Watermap spheres were displayed as + icons, and now correctly show colored spheres
  • When 3D Viz is drilling down from the sequence viewer, selecting another entity in the sequence viewer does not reset the existing residue selection in the sequence viewer and 3D Viz.
  • Double-click on a residue in the hierarchy to zoom to the residue on the 3D Canvas
• R-group Decomposition:
  • Identical scaffolds can no longer be added to a LiveReport. Scaffolds that have the same constitution, but distinct 2D coordinates and orientation, will be considered distinct scaffolds
• The Assay Viewer tool would crash if the table was sorted on a column that contained a null value, and now correctly sorts the values

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Hovering the cursor over an atom in the Workspace now simultaneously highlights its corresponding row in the Project Table and displays its row number in the Status Bar
• Improved defaults to “Get PDB Dialog” to auto display 2Fo-Fc diffraction data and auto set isocontours in EM maps to the Author recommendation
• Redesigned 2D Viewer Export with dedicated options dialog to control image size and support for high-quality SVG format for both single structures and HTML grids
• New Maestro Assistant (beta) – An AI-powered conversational interface providing context-aware help via the Schrödinger Knowledge Bot and enabling natural language styling command execution within the 3D workspace (documentation)

Force Field

• Updated FFBuilder default reference method to the MPNICE potential
  • Roughly 5x faster for typical chemistries
  • 20x faster for boron, bromine, iodine and silicon containing compounds

Target Validation & Structure Enablement

Protein Preparation

• Protein Preparation Wizard interactive jobs now save temporary files under a named folder in the Maestro working directory

Protein X-Ray Refinement

• Improved defaults to “Get PDB Dialog” to auto display 2Fo-Fc diffraction data and auto set isocontours in EM maps to the Author recommendation
• Redesigned GlideMap panel to dock ligands into maps generated from X-ray data by GlideXtal

Cryo-EM Model Refinement

• Redesigned GlideMap panel replaces the GlideEM panel with more granular options for fitting small molecule ligands into cryo-EM density maps

IFD-MD

• New Template Ligand Finder for ligand-binding mode prediction and cryptic binding site identification (Beta): Rapidly identify and visualize homologous proteins based on both protein and ligand similarity to uncover potential template ligands as references for IFD-MD

Binding Site & Structure Analysis

Mixed Solvent MD (MxMD)

• Enhanced cryptic binding site identification with updated in silico workflow (Beta): New workflow combining mixed solvent molecular dynamics (MxMD) with SiteMap to reliably reveal and detect cryptic binding sites

Hit Identification & Virtual Screening

Docking

• Optimized Glide which is nearly 2x faster than Glide is now the default method
• Revamp of the Glide WS MMGBSA correction

Ligand Preparation

Macrocycles

• Add command-line options to restrain cis/trans isomerism during alignment with tug_align.py
• Add a command-line option to tug_align.py to control MCS search algorithm timeout
• Small performance improvements to PrimeMCS

ABFEP

• Automatic membrane placement for AB-FEP simulations

Lead Optimization

FEP+

• New Settings interface that replaces the Advanced Options interface for more intuitive and easy simulation set up
• Clear predictions for RB-FEP edges
• Similarity Score column displayed in the analysis tab
• Batch delete and download multiple jobs with enhanced usability of the ‘Web Services Jobs Table’ panel
• Extend Atom Mapping to matched R-groups

Constant pH Simulations

• Improved panel usability and layout
• Added support to run constant pH simulations via Web Services

FEP Protocol Builder

• Roughly 2X speedup in workflow through improved defaults
• Improved accuracy in generated FEP+ maps through exploration and scoring of submaps with Louvian clustering. Alternatively, users can input desired submaps
• New cost-optimal option using Pareto Selection of FEP-PB Models to generate the best value protocols
• Improved prediction accuracy of generated maps through FEP+ Groups support, where ligands with different protonation, tautomeric, and conformational forms will be grouped, enabling FEP Group corrections to be applied

Quantum Mechanics

• Predict Ames toxicity via a QM-based workflow following Leach et al. (2009)
• X-ray emission spectroscopy (XES) prediction is now available (command line only)
• Implemented nine new double hybrid functionals with RI-MP2: B2-PLYP, B2GP-PLYP, DSD-BLYP, DSD-PBEP86, PWPB95, B2K-PLYP, B2T-PLYP, DSD-PBEB95, MPW2-PLYP
• Wave function stability analysis automatically corrects SCF instabilities leading to a more stable wave function
• Predict Nucleus-Independent Chemical Shifts (NICS) with new workflow
• Optical rotation as a function of wavelength
• Employ MLFFs (machine learning force fields) by setting Level of Theory option
• MPNICE now supported in all Jaguar workflows that have supported use of QRNN

Life Science Education Content

• New Tutorial: Preparing Nucleic Acid Structures
• New Tutorial: Structure Visualization and Interaction Analysis in Nucleic Acids
• New Tutorial: Analyzing Binding Sites of Nucleic Acids with SiteMap
• New Tutorial: Small Molecule – Oligonucleotide Docking with Glide
• New Tutorial: Forming RNA – Ligand Interactions with Ligand Designer
• New Tutorial: Potency Predictions for RNA-Binding Small Molecules Using RB-FEP
• New Tutorial: Predicting Drug Residence Times from Unbinding Kinetics Simulations
• New Learning Path: Oligonucleotide Modeling
• Quick Reference Sheet: GlideMap

Biologics Drug Discovery

• Easily specify mutational variants to be modeled in MMGBSA Residue Scanning by uploading an input FASTA file
• Load, analyze and visualize in the MSV desired mutations specified in the MMGBSA Residue Scanning Panel by newly available export of variants to a FASTA file
• Macromolecular Pose Filtering supports multi-chain ligands when filtering based on data obtained from Hydrogen-Deuterium Exchange (HDX) experiments
• Added a predefined selection for the Vα-Vβ interface, located under the TCR Regions menu, to enable one-click selection of this key binding region
• New T cell receptor (TCR)-specific presets

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Defect Correction: (+DEFECT_FORMATION_ENERGY) Formation energy computed in the panel
• Finite displacement method for phonons (command line)
• Increased number of iterations and cycles for default setup
• Support for GBRV pseudopotentials by default

MS Surface

Product: MS SurfChem

• Desorption Enumeration: (+ASSOCIATIVE_DESORPTION) Option for associative desorption

Microkinetics

Product: MS Microkinetics

• Calculation of selectivity from Catalytic Reaction Analysis (command line)

Reactivity

Product: MS Reactivity

• Reaction Network Profiler: Support for Garza solvation entropy partition functions (command line)
• Nanoreactor: Improvements to elementary reaction network algorithms

KMC Charge Mobility

Product: MS Mobility

• Option to compute field-dependent mobility based on charge diffusion (command line)

Dielectric properties

Product: MS Dielectric

• Complex Permittivity: Option to apply custom fitting parameters
• Complex Permittivity: Display of predictions from multiple fits
• Complex Permittivity: Option to input a pre-equilibrated structure
• Complex Permittivity: Improved speed from KWW parameter calculations

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Support for custom reactions that modify bond orders (command line)
• Solid Electrolyte Interphase: Improved algorithm to track unpaired electrons

Crystal Structure Prediction

Product: Crystal Structure Prediction

• Crystal Structure Prediction: Simplified UI for improved UX
• Crystal Structure Prediction: All space groups shown in Advanced Settings

Advanced Force Field Applications

Product: MS FF Applications

• Machine learning force field support in QM and MD panels

Transport Calculations via MD simulations

Product: MS Transport

• Diffusion: Support for GPU calculations on driver host
• Ionic Conductivity: (+IONIC_CONDUCTIVITY) Workflow solution to predict ionic conductivity in liquids
• Thin Plane Shear: (+PLANE_SHEAR_VELOCITY_PROFILE) Reduced noise in velocity profile
• Thin Plane Shear: (+PLANE_SHEAR_VELOCITY_PROFILE) Direct calculation of viscosity velocity profile
• Thin Plane Shear: Improved control of shear area to avoid drift of slabs

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Speed up for assignment of the coarse-grained force fields for large systems
• Coarse-grained Mapping: GUI panel for automatic mapping of CG structures
• CG FF Builder: Automated addition of antifreeze water for MARTINI mapping
• CG FF Builder: (+CGFF_BUILDER_MARTINI_NPT) Support for NPT ensemble during the fitting of MARTINI force field parameters
• CG FF Builder: Support for encrypted force field parameters
• CG FF Builder: Support for loading output from CG Mapping as input

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Tooltip to visualize the training set chemical space
• MD Descriptors: Automated setup for label and number of components from input CSV

Formulation ML

Product: MS Formulation ML

• Support for the description of ingredients without SMILES strings
• Formulation ML: Visualization of model performance from the GUI
• Formulation ML: Option to export feature importance to CSV
• Formulation ML: Option to compute feature importance during training
• ML Model Manager: GUI for management of model and version information

Layered Device ML

Product: MS Layered Device ML

• OLED Device ML: Support for classification models

MS Maestro Builders and Tools

• Adsorption Enumeration: Improved adsorption for sterically hindered atoms
• Adsorption Enumeration: De-duplication for molecular adsorption
• Complex Builder: Title suggestions for sketched ligands based on IUPAC name
• Complex Builder: Build dimeric organometallic complexes
• Disordered System: Speed-up for snap-to-grid and amorphous modes
• Disordered System: Support for MLFF
• Meta Workflows: Support for MLFF
• Polymer: Setup for angles on coarse-grained polymer models

Classical Mechanics

• Complex Bilayer: (+COMPLEX_BILAYER_BUILDER) Model building solution for complex protein membrane systems
• Diffusion: Support for MLFF
• Polymer Crosslink: Speed up with improved crosslinking algorithms
• Electrolyte Analysis: Option to plot density distribution isosurface
• MD Multistage: Preset relaxation protocol for stiff polymers
• MD Multistage: Preset relaxation protocol to aid convergence in OPLS5
• MD Multistage: Option to choose electric field units
• MD Multistage: Option to view steps from the preset relaxation protocols
• MD Multistage: Support for MLFF
• Molecular Deposition: Support for MLFF
• Polymer Chain Analysis: Improved speed on searching for backbone atoms
• Prepare for MD: Support for MLFF
• Radial Distribution Function panel restored for user access
• Visualize Restraints: Tool to show restraints in systems for MD simulations

Quantum Mechanics

• Adsorption Energy: Support for MLFF
• Beta Elimination: Support for MLFF
• Bond and Ligand Dissociation: Molecular formulas printed for fragments
• Nanoreactor: Support for MLFF
• Optoelectronic Film Properties: Option to calculate the reorganization energies for ISC/RISC
• Optoelectronic Film Properties: Option to plot the distribution of singlet-triplet splittings for ISC/RISC in the viewer panel
• Probe Grid Scan: Support for MLFF
• Reaction Energetics Enumeration: Support for MLFF
• Reaction Network Profiler: Support for MLFF

Materials Science Education Content

• New Tutorial: Machine Learning Force Field
• Updated Tutorial: Nanoreactor
• Updated Tutorial: Organometallic Complexes
• Quick Reference Sheet: MLFF Calculations
• Quick Reference Sheet: ML Model Manager
• Quick Reference Sheet: Coarse-Grained Mapping
• Quick Reference Sheet: Visualize Restraints
• Quick Reference Sheet: Welcome Screen
• Licensing information displayed in panel help documentation (example)
• Materials Science Panel Explorer: Filter for panels that support MLFF (go to Panel Explorer and select “Machine Learning Force Fields” under Methodology)

Education Content

Life Science

• New Tutorial: Preparing Nucleic Acid Structures
• New Tutorial: Structure Visualization and Interaction Analysis in Nucleic Acids
• New Tutorial: Analyzing Binding Sites of Nucleic Acids with SiteMap
• New Tutorial: Small Molecule – Oligonucleotide Docking with Glide
• New Tutorial: Forming RNA – Ligand Interactions with Ligand Designer
• New Tutorial: Potency Predictions for RNA-Binding Small Molecules Using RB-FEP
• New Tutorial: Predicting Drug Residence Times from Unbinding Kinetics Simulations
• New Learning Path: Oligonucleotide Modeling
• Quick Reference Sheet: GlideMap

Materials Science

• New Tutorial: Machine Learning Force Field
• Updated Tutorial: Nanoreactor
• Updated Tutorial: Organometallic Complexes
• Quick Reference Sheet: MLFF Calculations
• Quick Reference Sheet: ML Model Manager
• Quick Reference Sheet: Coarse-Grained Mapping
• Quick Reference Sheet: Visualize Restraints
• Quick Reference Sheet: Welcome Screen
• Licensing information displayed in panel help documentation (example)
• Materials Science Panel Explorer: Filter for panels that support MLFF (go to Panel Explorer and select “Machine Learning Force Fields” under Methodology)

LiveDesign

What’s New in 2025-3

• Freeform Columns
  • The Freeform column user interface to define picklist values has been redesigned to facilitate faster picklist value creation
  • Upload 3D attachments to a Freeform column (‘pse’, ‘mae’, ‘maegz’, ‘mmtf’, ‘pdb’, ‘pdbgz’, ‘sdf’) and view them in the 3D Visualizer
• Plots
  • Pinned tooltips are included in plot exports
  • Box plots now permit horizontal and vertical overlays
• Advanced Search
  • “Case-insensitive” and “Match any” options are now available as gear options in Advanced search queries
  • The “Real” and “Virtual” quick filter options are now available for all entity types in the Advanced search panel
  • Scrolling is now enabled while running auto-update advanced search. Pointer actions for individual search conditions and the top of the drawer are disabled
• Sequence Viewer
  • View the chemical structure for non-natural residues with docked tooltip
  • Residues that match the corresponding reference residue can be represented as dots(.) instead of letters, to more easily identify differences
  • Drag selection now extends during click and drag until the end of the canvas
  • Data columns section in the sequence viewer now auto opens if we toggle the data columns checkbox in the collapsed state
• Data & Columns Tree
  • Published limited assay columns are now searchable via the [LIM] prefix in the D&C tree and typing the complete column name searches and highlights the respective column
• Import
  • Admin users can define any existing user as ther “Lot Scientist” for an entity using LDClient with the following requirements: 1) the username must exactly match an existing username in LiveDesign; new usernames cannot be created and other strings cannot be used, and 2) the Lot Scientist can only be defined when registering a new entity, and cannot be updated for existing entities
• Admin Panel
  • Admin users can update the ENABLE_TECHNICAL_USERS property to show Technical users within user lists
  • Bulk kill up to 40,000 tasks in Task Engine
• UX Improvements
  • The one-click “View in Maestro” link has been redesigned to more clearly separate the “View in 3D” and “View in Maestro” options
  • Sorting icons on the column headers have been updated
  • Columns that are filtered in the LiveReport now show a filter icon on the column header
  • The confirmation dialog for copying compounds from one LiveReport to another has been removed
  • Admin users can configure the number of entities that can be viewed simultaneously in the 3D visualizer by defining the MAX_LOADED_3D_STRUCTURES property
  • Column headers remain visible when scrolling within the Stereoisomer tool

What’s Been Fixed

• Admin Panel
  • License files would occasionally fail to upload in the Admin Panel UI, and now correctly upload
  • Models would show hyper-restricted projects as an optional project to add the Model to, even though the Protocol did not include the hyper-restricted project. The Models page now only shows the projects that are included in the Protocol
• Freeform columns
  • Picklist Freeform columns would show incorrect coloring rules if a picklist value was selected that contained a newline, and now show the correct colors
  • Creating a Comment Freeform column would fail if the column name matched the title of any other column in any other LiveReport, and now succeeds, unless the column name matches an existing published Freeform column title
• Filters
  • Toggling off filters on a LiveReport would show flashing cells until the browser was refreshed, and now shows the correct cell values’
• Forms
  • Copying text from a widget in Forms would fail if the widget was configured as a drilldown widget, and now text can be copied from drilldown widgets
  • Characters would occasionally get deleted while typing in the Forms annotation widget, and now do not get deleted
• Formulas
  • Formulas returning multiple values would not show values when a if() function was used, and now correctly shows multiple values
• Ligand Designer
  • Ligand Designer: reference ligands using a .maegz format would not show up in the 3D visualizer, and now correctly show up in the 3D Visualizer
• Limited Assay Columns
  • Pasting strings into the Create Limited Assay Column dialog would briefly appears, but then disappear, and now remains visible in the dialog
• LiveReports
  • Clicking a LiveDesign hyperlink would fail to open the linked LiveReport, and instead would open the user’s last-opened LiveReport; clicking hyperlinks now correctly opens the linked LiveReport
  • Copying a LiveReport from one project to another would fail when the LiveReport contained a “Presence in LiveReport” Advanced Search condition, and now succeeds.
• Templates
  • Applying a template to a LiveReport would not show the applied filters unless the browser page was refreshed, and now correctly shows the applied filters
• The “Give Feedback” button has been disabled

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• New Welcome Screen on startup provides quick access to common tasks such as creating and opening projects and importing structures
• Modernized and streamlined Project Table for enhanced usability
  • New Table Configuration pane allows fast switching between Light and Dark themes and toggles visibility of the ePlayer and Property Tree.
  • New Gadgets Menu provides convenient access to Charts and the 2D Viewer
• New Workflow Action Menu (WAM) to view spectroscopy results from Jaguar and Jaguar Spectroscopy calculations in the Project Table

Target Validation & Structure Enablement

Protein Preparation

• Improved minimization protocol to support broader coverage of biological and chemical systems
• Produce more reliable prepared structures by expanded coverage of equivalent tautomeric ligand states
• More easily view serious structural issues by filtering diagnostic reports with a severity threshold
• New ‘Missing Atom’ tab on the Diagnostics panel enables select sidechain and loop modeling

Cryo-EM Model Refinement

• GlideEM poses are now sorted by GlideScore which is more discriminating in ranking low RMSD structures than Denscore

Ligand Preparation

Ligand Docking

• Faster Glide scoring and docking with optimized Glide (Beta): Screen larger libraries and find better candidates with optimized Glide, including enhanced Active Learning Glide and Python API support
  • Same industry-leading Glide docking funnel and scoring functions, Emodel and GlideScore
  • Faster turnaround with same compute resources for Active Learning Glide and AutoDesigner
  • Advanced Python API support offers easy automation and file control over docking process for greater experimentation
  • Accessible through the new Ligand Docking panel that enables setup of Active Learning and Glide calculations

ABFEP

• Energy Decomposition data is now reported in Analysis PDF reports

Lead Optimization

FEP+

• New FEP+ Pose Builder workflow for automatically generating high-quality ligand alignments (Beta): Generate FEP-ready poses faster and run FEP+ at scale with an automated workflow designed for unbiased selection and robust atom-mapping
• Ability to read and write FEP+ Protocol files directly in the FEP+ Panel
• Improved Classification matrix styling
• Kendall’s tau statistic added to the statistical metrics reported
• Improvements to exported FEP+ data in csv/xls formats
• Added ‘None’ as a new Hot Atom Rule

Protein FEP

• FEP+ Residue Scan supported in Protein FEP+ for Ligand Selectivity panel

Constant pH Simulations

• Added support for Cysteine residues

FEP+ Protocol Builder

• Sharply reduced compute resources to run default workflow by shrinking initial simulation times to 0.5 ns and extended times to 10 ns
• Seamless interconnection as FEP+ Panel can now Read/Write Protocol Builder files
• Bias the selection of protocols to extend including compute efficiency via Pareto analysis (command line only)
• Added support for covalently bound ligands
• Ability to optionally sample charge states of GLU, ASP, LYS, ARG, and CYS in protocol optimization

De Novo Design

AutoDesigner – R-group Design

• New R-group Similarity score feature to focus ideation around compounds of interest
• New Design Rationale capability to improve ADME endpoints with respect to reference ligands

Alternative Modalities

Bifunctional Degraders

• Expanded support for protein degrader modeling with the new Degrader Sampling Workflow (Beta): Generate accurate degrader ternary complexes through integration of protein-protein docking and linker sampling in a structure-based workflow

Biologics Drug Discovery

• Augmented AI/ML capabilities for biologics with machine learning-based T-Cell Receptor (TCR) structure prediction (Beta): Perform high throughput structure prediction and large scale modeling of TCRs with the ImmuneBuilder deep learning model and Prime
• New Macromolecular Pose Filtering panel to filter native or near native poses from an ensemble of complexes using experimental data such as HDX-MS

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• A new environment variable for the location of Quantum ESPRESSO binary

Transport Calculations via MD simulations

Product: MS Transport

• Thin Plane Shear: Selection of slab region by molecular units

KMC Charge Mobility

Product: MS Mobility

• Compute KMC Charge Mobility: Predictions based on Schrödinger’s new mobility engine

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Updates to existing models
• Machine Learning Property: Prediction of triplet reorganization energy
• Machine Learning Property: Prediction of S1-to-T1 energy gap (∆EST)
• Machine Learning Property: Predictions from the interactive mode automatically added to the Project Table
• MLFF Calculations (Beta): Single-point energy and geometry optimization tool using Schrödinger’s latest machine-learned force fields

Formulation ML

Product: MS Formulation ML

• Formulation ML: Support for custom ingredient descriptors
• Formulation ML: Support for creating models using multiple CPUs in parallel
• Formulation ML: Support for setting mixtures as individual components
• Formulation ML Optimization: Workflow solution to optimize materials formulations

Layered Device ML

Product: MS Layered Device ML

• OLED Device ML: Workflow solution to predict OLED device performance
• Optoelectronic Device Designer: Use ML OLED device models to predict performance

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Automated CG Mapping: (+AUTOMAPPING_MARTINI_PROTEIN) Support for proteins in automated mapping and parameterization for Martini
• Automated CG Mapping: Accurate mapping for carbohydrate systems
• Improved threshold for momentum errors in CGMD simulations
• CG FF Builder: Parameters for water-water interactions fixed by default

Dielectric properties

Product: MS Dielectric

• Complex Permittivity: Option to run replicates in parallel

Reactivity

Product: MS Reactivity

• Reaction Network category created under the Materials task menu
• Reaction Workflow renamed to Reaction Network Profiler
• Auto Reaction Workflow renamed to Reaction Network Enumeration Profiler
• Reaction Network Profiler: Option to run conformational search using CREST
• Reaction Network Profiler: Conformational search included in restarts (command line)
• Nanoreactor: Option to screen products by energy relative to reactant state
• Nanoreactor: (+ELEMENTARY_REACTION_NETWORK) Support for the Elementary Reaction Network workflow

Microkinetics

Product: MS Microkinetics

• Microkinetics Deposition Analysis: Workflow solution to run post-analysis of microkinetic simulations in deposition or etch processes of solid materials
• Microkinetic Modeling: (+MATSCI_MKM_INTERACTIONS) Support for simple quadratic adsorbate-adsorbate interactions

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Option to block intramolecular reactions (command line)
• Solid Electrolyte Interphase: Option to use DFT charges for new species

Crystal Structure Prediction

Product: Crystal Structure Prediction

• Crystal Structure Prediction: Interface and workflow to predict crystal structures and polymorphs for a given molecular compound

MS Surface

Product: MS SurfChem

• Adsorption Enumeration: Access to workflow assessing reactive adsorption
• Desorption Enumeration: Workflow solution for assessing desorption of multiple molecules

MS Maestro User Interface

• Direct link from the task menus to Materials Science Panel Explorer page

MS Maestro Builders and Tools

• Structured Liquid: Automatic standardization of custom lipids
• Polymer: Improved dihedral setups for multiple shortest-length backbones
• Organometallic Conformational Search: Option to run conformational search using CREST

Classical Mechanics

• Evaporation: Option to export the results as CSV file
• MD Multistage: Center of mass motion removed for coarse-grained systems
• Thermophysical Properties: Option to save trajectory energy file
• Umbrella Sampling (Beta): Workflow solution for umbrella sampling of membranes

Quantum Mechanics

• Adsorption Energy: Support for reactive adsorption and desorption energies
• Adsorption Energy: Improved assessment of entropy loss during the adsorption
• Bond and Ligand Dissociation: Option to set product charges from formal atomic charges
• Bond and Ligand Dissociation: Support for PCM and SMD solvent models
• Bond and Ligand Dissociation: Improved 2D visualization of charges and radicals in product fragments
• Crest: UI for semiempirical QM based conformational search using CREST
• Optoelectronic Film Properties: Support for multiple reorganization energies as input for computing intersystem crossing (ISC) rate
• Optoelectronic Film Properties Viewer: Support for user-input reorganization energies to instantly re-evaluate SEET rate
• Thermochemistry Viewer: Support for viewing reactive adsorption and desorption energies
• Trajectory Density Analysis: Improved naming scheme for atom groups

Education Content

Life Science

• New tutorial: Exploring Protein Binding Sites with Mixed-Solvent Molecular Dynamics
• New tutorial: Introduction to T-Cell Receptor Modeling with BioLuminate
• Updated tutorial: Antibody Visualization and Modeling in BioLuminate
• Updated tutorial: Peptide Modeling with BioLuminate
• Updated tutorial: Target Analysis with SiteMap and WaterMap
• New QRS: Structure Reliability Report
• New QRS: Custom Reactions for Covalent Docking
• New QRS: Mixed-Solvent Molecular Dynamics
• Updated QRS: GlideWS Model Generation
• Updated QRS: MM-GBSA Residue Scanning

Materials Science

• New Tutorial: Umbrella Sampling
• New Tutorial: Crystal Structure Prediction
• New Tutorial: Optimization of Formulations Using Machine Learning
• New Tutorial: Machine Learning for OLED Device Design
• New Tutorial: Nanoemulsions with Automated DPD Parameterization
• New Tutorial: Applied Machine Learning for Formulations
• Updated Tutorial: Atomic Layer Deposition
• Updated Tutorial: Design of Asymmetric Catalysts with Reaction Network Enumeration Profiler (previously AutoRXNWF)
• Updated Tutorial: Machine Learning Property Prediction
• New QRS: CREST
• New QRS: Microkinetics Deposition Analysis

LiveDesign

What’s New in 2025-2

• Import Antibody-Drug Conjugates from SimpleSchema
• Freeform Columns
  • New “Comment” type: Write threaded conversations within a Freeform column, and track usernames and timestamps
  • Creating a Freeform column is now performed using a wizard that permits selecting the data type of the Freeform column first, and then specifying the Freeform column details
• Formulas
  • Formulas support multiple values: Input cells to formulas can now contain multiple valuesFormulas can output multiple values, aligned by Experiment, Lot, or Pose. New formula functions were created to handle input cells with multiple values: cellAggregation(), join(), any(), and all()
  • Failed model cells can now be used as formula input
  • A new isFailed() function returns true for any failed model cells, and false otherwise
• Dashboards (Previously called Landing Pages)
  • Biologics and Generic entities are now supported on Landing Pages
  • Project Admins can edit the project description directly on Landing pages instead of configuring it from the Admin panel
  • Project admins can now select a date range via the ‘Time range’ filter in Landing Page Entities Section to look for entities added within a range of days
  • A ‘Bookmark LiveReport…’ option has been added in the LR grid menu and clicking on the option redirects the user directly to the new Bookmark page (in Landing pages) in a new window. The LiveReport’s name gets auto-populated in the LiveReport info section of the window
• Admin Panel: Add multiple new users at once with a CSV upload
• Sequence Viewer
  • Perform sequence-activity relationship analyses by viewing multiple data columns in the sequence viewer
  • Select a reference sequence even when there’s no alignment
  • Retry failed alignments and cancel running alignments
• Unification of Generic Entity and Biologics Import Pipeline: Generic Entity and Biologics import tabs are collapsed into “Biologics/Others” tab. All entities imported from “Biologics/Others” tab are virtual entities. Allows csv import of metadata on virtual entities.
• UX Improvements
  • R-group Decomposition highlighting can now highlight the bond lines, rather than showing a halo-style highlighting around the bond
  • Users now have the quick filter options to filter by any/all types of Entities on Advanced search, just like in the Filter panel. They can choose from the options of All, Compound, R-group, Biologic and GE
  • Users can now drag a compound structure to Advanced search to create a new substructure query, like in Filter panel
  • Export data qualifiers (e.g., the greater than symbol ‘>’) as a separate column in data exports
  • Exporting a LiveReport: Choose whether to include filtered out rows, or exclude them, when exporting via the User Interface or LDClient
• Structure Processor: A new “STRICT” processor setting allows compounds with valence violations and other invalid chemistries to be accepted or rejected by the processor. By default, compounds with valence violations are not permitted

What’s Been Fixed

• Data and Columns Tree
  • Attempting to favorite published Limited Assay Columns in the Data & Columns Tree would fail, and now those columns can be favorited
• Filters
  • LiveReport filters in Complex view would show additional brackets to the filter conditions, and the filter conditions would rearrange, when columns were removed from LiveReports. The arrangement of filter conditions are now properly retained and brackets do not appear
  • Removing a column from a LiveReport while viewing the Filter panel would change the Filters view from simple mode to complex mode, and now keep the view in simple mode
  • Filtering out a frozen row would show flashing squares in the first row in the main spreadsheet, and now correctly shows that row’s data
• Forms
  • Copying text from a Forms widget previously showed dotted lines in multiple widgets, and incorrectly indicated that text from multiple widgets was copied. Dotted lines now appear only around the cells within a single widget that were most recently selected
  • Forms annotation widgets would not persist styling changes (e.g., font color), and now correctly persist the changes
  • Matrix widgets included excess whitespace around values; the minimum row height has been reduced to eliminate excess whitespace
  • Viewer users could not see 3D results in the 3D Visualizer nor in Forms, and now can view 3D results
• LiveReport Management
  • LiveReport tabs would disappear after logging out and logging in, and now correctly appear after logging back in
  • Clicking a LiveDesign hyperlink would fail to open the linked LiveReport, and instead would open the user’s last-opened LiveReport; clicking hyperlinks now correctly opens the linked LiveReport
  • The Create New LiveReport dialog now permits filtering the list of LiveReport templates
  • Attempting to apply a template to a LiveReport that contained filters would fail, and now applying a template succeeds
  • Overwriting a template would create a new template, instead of overwriting, and now correctly overwrites the template
  • Applying a template to a LiveReport would not include Limited Assay Columns contained within the template, and now correctly include Limited Assay Columns
  • Duplicating a LiveReport would not include all columns by default, and now includes all columns by default
• Maestro Upload
  • Importing structures into Maestro from LiveDesign would occasionally fail when task status of “FINISHED” was reported before the result URL was available, and now correctly imports structures
  • Importing structures into Maestro from LiveDesign would fail if a LiveDesign model returned an empty protein file, and now the empty protein file will be skipped and not imported into Maestro
• Model Creation
  • Configuring a Protocol in the Admin Panel to use a ${RDKIT-MOL} macro would prevent the creation of a parameterized model in the LiveDesign UI, and now correctly allows creating a parameterized model
• Plots
  • Plot tooltips could not be dragged and moved after pinning to the screen, and now can be dragged to a new position after pinning
• R-group Decomposition
  • Reordering R-group Decomposition scaffolds would eliminate coloring rules and sorting rules for R-group columns, and now correctly maintains coloring rules and sorting rules
• Search
  • Advanced Search would occasionally return extra entities that didn’t match the search conditions on columns, when those columns had an undetermined data type, and now does not return extra entities
• Sequence Viewer
  • Horizontally scrolling the sequence viewer would reset the ruler, and show the wrong residue numbers at the top, and now shows the correct residue numbers
• User Administration
  • User email addresses would not save in LiveDesign when using Single Sign-on, and LiveReport notifications would not be emailed to users. Email addresses and are now correctly saved
  • Welcome emails for new users would include an incorrect LiveDesign URL, and now include the correct URL

Small Molecule Drug Discovery

Target Validation & Structure Enablement

Protein Preparation

• Improved peptide bond connectivity by better integration of sequence information in the Protein Preparation Workflow (PPW)

Protein X-Ray Refinement

• Phenix/OPLS can now run from CIF files containing reflections

Cryo-EM Model Refinement

• Improved support of macrocycles in GlideEM/GlideXtal

Binding Site & Structure Analysis

Binding Site Characterization

• Rationalize kinase selectivity challenges using the Kinase Conservation Analysis Interface that combines sequence and complex structural information: Identify promising selectivity handle residues to modulate ligand kinase selectivity that can be tested with FEP+ Residue Scan

Desmond Molecular Dynamics

• Optimize the unbinding kinetics of protein-ligand complexes using dissolution rate predictions based on unbinding pathways identified by enhanced sampling methods

Mixed Solvent MD (MxMD)

• Identify potential binding sites and assess drugability of competitive and allosteric binding sites with the full release of a Mixed Solvent Molecular Dynamics Interface to setup and analyze MxMD simulations

Hit Identification & Virtual Screening

Active Learning Applications

• Improved diversity of top scoring ligands in Active Learning ABFEP by using 3D features extracted from Glide poses in ML model building
• Researchers can now specify different batch sizes and selection rules to exploit or explore for each iteration in Active Learning simulations

Lead Optimization

Protein FEP

• View trajectories and structural output from FEP+ Residue Scans in the FEP+ interface
• Rationalize key interactions in ligand binding using per-contact residue interaction energy analysis which is new for ABFEP
• Easily identify disconnected sub-maps in a busy FEP map

Spectroscopy

• More accurate NMR spectra predictions by identifying magnetically inequivalent nuclei

Macrocycles

• Automatically enumerate and cyclize peptide sequences from FASTA files with the new cyclize_peptide.py script
• Ring template generation for Glide macrocycle docking with bespoke parameters is now automated by the macrocycle_template_gen.py script
• An updated macrocycle_sample.py script with greater control of sampling options and a new receptor-aware macrocycle sampling algorithm that includes surrounding receptor atoms to restrict conformational search space
  • Updated macrocycle_sample.py script replaces macro_sample.py
• Improved handling of ring nitrogen atom substituents during ring template conformation generation
• tug_align.py now supports 2D ligand files as inputs
• tug_align.py exposes several new command-line options that allow finer control of the alignment convergence criteria which are useful in reducing convergence times for large molecules such as cyclic peptides

Medical Chemistry Design

Ligand Designer

• Enable user-specificed or automatically generated ligand protonation and tautomeric states from the 2D/3D editing workflow for MCS Docking

Biologics Drug Discovery

• Completely rewritten MMGBSA Residue Scanning backend that is more reliable and has improved support for a wider variety of non-standard amino acids and mutation of DNA/RNA
• New high-throughput, machine learning-based antibody and nanobody structure prediction with ImmuneBuilder. With throughput of about one minute per structure, it is suitable for batch modeling of thousands of structures
• Automatically identify and annotate for visualization TCR alpha and beta chains from a FASTA file (commandline run_tcr_modeling.py)
• Updated N-glycosylation PROSITE pattern that is less restrictive

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Workflow solution to calculate the defect energy
• Workflow action menu (WAM) for output from periodic DFT convergence test
• Support for setting total magnetization/charge for each structure
• Support for computing thermodynamic properties via dynmat.x (command line)
• Support for stopping an NEB calculation and returning intermediate structures

Materials Informatics

Product: MS Informatics

• Formulation ML: Option to control advanced settings
• Machine Learning Property: Skip structures outside the model scope
• Machine Learning Property: Prediction of singlet (S0) to triplet (T1) energy
• Machine Learning Property: Prediction of hole / electron reorganization energy
• Machine Learning Property: Prediction of orbital (HOMO / LUMO) energy
• Machine Learning Property: Updates to existing models

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Automated CG Mapping: Mapping MARTINI for speciality chemicals / polymers
• CG FF Builder: Support for exporting atomistic reference data

Dielectric properties

Product: MS Dielectric

• Complex Permittivity: Linear fitting parameter retained during exponential fitting

Reactivity

Product: MS Reactivity

• Nanoreactor: Control over thermostat bath temperature
• Nanoreactor: Support for parallelization of xTB dynamics simulations
• Reaction Workflow: Support for the use of the xTB Hessian for transition states
• Reaction Workflow: Use of input conformers when conformation search fails
• Reaction Workflow: Improved SCF convergence for energy calculations

Microkinetics

Product: MS Microkinetics

• Microkinetic Modeling: Improved speed/scalability by up to 2 orders of magnitude
• Microkinetic Modeling: Improved model for multiple catalysts / catalyst site types
• Microkinetic Modeling: Improved data visualization in the viewer
• Microkinetic Modeling: Job name shown in the viewer

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Improved subjob queuing coordination
• Solid Electrolyte Interphase: Support for constant pressure (NpT) simulations (command-line)

MS Maestro Builders and Tools

• GUI panel to digitally design, manage, and visualize OLED devices
• Single Complex: Improved UI for better usability
• Solvate System: Support for generating multiple configurations by random seeds

Classical Mechanics

• Workflow solution to compute thin plane shear friction
• Barrier Potential for MD: Support for reading barrier information from entry
• Evaporation: Option to plot total number of molecules removed from the system
• Evaporation: Information tied to barriers (when applied) logged in the output
• Polymer Crosslink: Improved speed by efficient checking for ring spears
• Trajectory Density Analysis: Option to display multiple density depths
• Trajectory Density Analysis: Export option for 2D heat-map plot

Quantum Mechanics

• Workflow solution to plot phase diagrams based on energy
• Workflow solution to compute and analyze computational ellipsometry data
• QM Convergence Monitor: Easy access to the structure from the last step

Education Content

Life Science

• New tutorial: Refining crystallographic protein-ligand structures using GlideXtal and Phenix/OPLS

Materials Science

• New tutorial: Automated Martini Fitting for Coarse-Grained Simulations
• New tutorial: Thin Shear
• New tutorial: Defect Energy Calculation
• New tutorial: Optoelectronics Device Designer
• New tutorial: Computational Ellipsometry
• New tutorial: Phase Diagrams
• New tutorial: Ab initio Molecular Dynamics Simulations of Li-ion Diffusion in Solid State Electrolytes
• Updated tutorial: Microkinetic Modeling
• Updated tutorial: Organometallic Complexes

LiveDesign

What’s New in 2025-1

• Biologics
  • Forms view now require the Sequence Viewer to drilldown from another widget
  • Performing a sequence alignment now shows an alert indicating the type of Alignment, and provides a “Try Again” button if the alignment fails
  • Forms views that contain both a Sequence Viewer and 3D Visualizer permit a synchronized selection of amino acid residues, such that selecting an amino acid in the Sequence Viewer will highlight the amino acid in the 3D Visualizer, and vice versa
  • Sequence search options now permit searching the Database, Active LiveReports, and Other LiveReports
  • View non-natural amino acid molecular structure in a tooltip by hovering over residues in the sequence viewer
  • Toggle monomers’ display format in the sequence viewer to view either single-letter FASTA format, or a custom symbol for non-natural monomers (up to 6 characters)
  • Reset Gap Penalties, Numbering Scheme, and Scoring Metrics to their default values for each alignment method
  • Substructures searches in Advanced search panel support a “Match by Child” option, which enables searching against an entity’s subcomponents
• Performance Improvements
  • Small Molecules uploaded from file imports, enumeration, and Maestro uploads appear in the LiveReport more quickly
• Landing Page: View all of a compound’s experimental data on the Compound’s detail page
• Data and Columns Tree:
  • Group Multi-Parameter Optimization columns and Formulas columns into folders
  • The button text to create new Formulas, MPOs and FFCs has been changed from “NEW” to “CREATE”
  • Published Limited Assay Columns now show the [LIM] prefix in the Data & Columns Tree
• A new MAE-FILE macro for Protocols in the Admin Panel allows Protocol and Models to access compounds and biologics using a Maestro file format. The Maestro file format includes residue information for Biologics
• Configure LiveDesign to send an email on usage statistics, including: the number of unique logins over the last month, total number of active users, Number of compounds added last week, total number of compounds, total number of LiveReports updated last week, total number of active LiveReports and number of active LiveReports. For each user, the following information is reported: username, date of first login, date of last login, number of owned LiveReports
• Configure a server-wide search setting to set the default searching behavior in the search panel to the Database, the Active LiveReport, or Other LiveReports
• A new LDClient method, get_all_compounds(), enables retrieving all compounds within a specified list of projects
• Sketched reactions within the Reaction Enumeration tool can now use atom queries to add greater specificity to the reaction definition

What’s Been Fixed

• Updating a LiveReport template would create a duplicate template, and now correctly updates the template
• Model columns that were used as inputs to more than 65,536 columns would fail to calculate values for new compounds, and now correctly calculate and display the predicted values
• Pasting into the sketcher would fail on Windows when touchscreen was enabled, and now correctly pastes structures
• LiveReports with hundreds of formula columns would show flashing cells, and slow down other LiveReports, but now correctly calculate and do not affect other LiveReports’ performance
• Formulas that used the combine() function could not be used as input to subsequent formulas, and the formula would fail to calculate. Formulas using the combine() function now correctly calculate when they are input to other formulas
• Selecting rows in the main spreadsheet would not show the 3D structure in the 3D Visualizer, and now correctly shows the 3D structure
• LiveReports would show red error bars when multiple input values to a parameterized model changed simultaneously in the spreadsheet, and now the LiveReport loads correctly
• The tautomer deduplication logic previously deduplicated keto-enol tautomers, but caused an unintended side effect of deduplicating compounds that were not tautomers. The updated tautomer deduplication logic has been reverted to the old behavior found in LiveDesign version 2024-4 and earlier
• Popping out a model column’s cell that contained and image would open two tabs in the browser (one tab with the image, and one blank tab), and now only opens a tab with the image
• Previously, changes to gap penalties were not persisting when saved in the Forms view, and now gap penalty values will persist correctly upon modification and saving
• The “Batch Create Limited Assay Columns” option previously was unavailable in the column menu, if the column was within a column group, and now the option always appears
• The residue synchronization between the 3D Visualizer and Sequence Viewer now remains functional even after changing the numbering scheme in Sequence Viewer
• Model results would occasionally appear as Failed in the LiveReport, when in fact the model ran successfully, and now model results correctly show results in the LiveReport
• The Assay Viewer Tool would occasionally change the date filter to 0 days and would not show data, and now defaults to showing data that was uploaded within the previous day.
• Model results would occasionally appear as Failed in the LiveReport, when in fact the model ran successfully, and now model results correctly show results in the LiveReport
• Ligand Designer’s deleted poses would occasionally reappear, and now no longer reappear
• Protocols and Models showed their created date as one day earlier than their actual created date, and now show the correct date
• LiveReport filters did not support filtering for Real or Virtual Biologics, and now provide quick toggles to apply those filters
• Opening a model attachment from the main spreadsheet (e.g., a LID from a Glide model) would fail to show the image, and now correctly shows the image
• Plot tooltips could not be dragged and moved after pinning to the screen, and now can be dragged to a new position after pinning
• Importing a biologic entity would occasionally not show its subcomponents in the main spreadsheet, and now will correctly show its subcomponents
• LiveDesign would occasionally fail to open LiveReports due to a database lock, and now no longer will freeze
• Filtering out a frozen row would show flashing squares in the first row in the main spreadsheet, and now correctly shows that row’s data
• The sequence viewer would show all entities in the LiveReport, even when only one entity was selected, and now correctly shows only the selected entities
• Horizontally scrolling the sequence viewer would reset the ruler, and show the wrong residue numbers at the top, and now shows the correct residue numbers
• Opening the Project Picker would occasionally take several seconds to show the list of projects, and now shows the list of projects immediately
• LiveDesign would occasionally fail to open LiveReports due to a database lock, and now no longer will freeze
• Filtering out a frozen row would show flashing squares in the first row in the main spreadsheet, and now correctly shows that row’s data
• Exporting a LiveReport defaulted to exporting a subset of columns, and now defaults to exporting all of the columns
• Syncing LiveDesign users with external authentication systems would fail because LiveDesign counted unlicensed users against the total license count, and now permits syncing users as long as there are available licenses
• License files would occasionally fail to upload in the Admin Panel UI, and now correctly upload
• User email addresses would not save in LiveDesign when using Single Sign-on, and LiveReport notifications would not be emailed to users. Email addresses and are now correctly saved
• LiveReport tabs would disappear after logging out and logging in, and now correctly appear after logging back in
• Duplicating a LiveReport defaulted to copying a subset of columns, and now defaults to copying all of the columns

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Improved usability in scatter plots and histograms:
  • See relationships in data across multiple plots and histograms with streamlined menu into “Entry Actions” and “Sync Options” menu icon
  • Added support for string and boolean histograms
• In the histogram panel, easily switch between settings and data table views
• Specify the number of columns and rows for fine control of Workspace Tiles
• Save animated GIF of vibrational motion from Jaguar frequency calculation
• Enhanced Cryo-EM surface performance:
  • Up to 2x faster loading of Cryo-EM surface files
  • Up to 5x increase in speed for isosurface contour creation and adjustments
• Refined toolbar design for enhanced simplicity, modern aesthetics, and optimization for dark mode
• Updated Maestro Project format to version 5:
  • Support for multi-letter chain names beyond traditional 26 characters
  • Compressed .prjzip files designed for easy sharing via email
  • Automatic conversion of version 4 projects to version 5 upon opening
  • By default save Maestro Projects in version 5 format with an option to save in version 4 for backward compatibility
• Support added for two new CIF file formats: “PDBx/mmCIF (*.cif)” and “Small Molecule CIF (.cif)”
• Opening Maestro locally from LiveDesign is now supported on macOS, Linux, and Windows
• Revamped splash screens & iconography: Modern visuals for an updated look and feel

Workflows & Pipelining [KNIME Extensions]

• LiveDesign Admin node can take user credentials from the LiveDesign Connection node enabling SSO configuration

Target Validation & Structure Enablement

Protein Preparation

• Protein The Protein Preparation Workflow now considers Epik states of ligands during the hydrogen-bond network optimization stage by default

Protein X-Ray Refinement

• New sf2map.py script quickly generates an aligned x-ray map, given an input structure and a cif file containing structure factors

IFD-MD

• Updated IFD-MD for automatic sampling of histidine tautomer states (HID, HIE): Consider induced fit effects simultaneously to resolve receptor tautomeric states and predict receptor and ligand conformations

Binding Site & Structure Analysis

SiteMap

• Automatically apply Combined Mode which breaks down sites larger than 800 Å3

Mixed Solvent MD (MxMD)

• Improved cryptic pocket identification with new mixed solvent molecular dynamics (MxMD) interface including customizable visualization (Beta): Gain a clearer understanding of candidate binding pockets on the protein surface with a new interface to set up and analyze MxMD simulations

Hit Discovery

Active Learning Applications

• Faster time-to-results in AL-Glide and Glide using ZeroMQ mode for machine learning evaluation stage and Glide docking stage

Shape Screening

• Additional similarity normalization schemes now available for Quick Shape and 1D Screening command. In addition to the max{O(A,A), O(B,B)} default can apply min{O(A,A), O(B,B)}, O(A,A), and O(B,B) where O(A,B) is the overlap between ligands A and B
• Run Quick Shape and 1D Screens against a Phase pharmacophore hypothesis as the query
• Improve speed of Quick Shape calculations with -limit and -NJOBS1D options that enable more efficient utilization of compute resources

Glide

• Full release of Glide WS mode, previously known as WScore, to prioritize ligands for improved hit enrichment and pose prediction accuracy
  • Leverages explicit water energetics to enhance the accuracy of protein-ligand poses and reduce experimentally inactive compounds in top-scoring virtual hits

Lead Optimization

FEP+

• Gain deeper insights into receptor-ligand interactions with new Per-Residue Energy Decomposition in FEP Edge analysis
• Perform categorical analysis in the Correlation Plot (FEP+) interface using classification matrices including common metrics such as Accuracy, Specificity, Recall, Precision, F1 Score, Cohen’s K and Kendall’s T
• View reason why compounds are skipped in ABFEP calculations in the FEP+ Panel

Protein FEP+

• Full release of Protein FEP+ Residue Scanning (with lambda dynamics)
  • Workflow now generates an FMP archive to be loaded in the FEP+ Panel
  • Web Services support

FEP+ Protocol Builder

• Ability to run with either OPLS4 or OPLS5 force field
• Added support for sampling of more residue protonation states
• New option to skip active learning and perform exhaustive exploration of protocol parameter space

Quantum Mechanics

• Return solvation entropy in implicit solvent calculations
  distributed_frequencies.py workflow for numerical frequency calculations
• Added support for isotope 11B in NMR calculations
• Implicit solvent model SMD now has gradients and frequencies
• E-sol now supports the CPCM-X implicit solvation method for rapid solvation energies (command line only)

Semi-Empirical Quantum Mechanics

• Updated xTB to version 6.7.1 which uses the advanced solvent model CPCM-X

Macrocycles

• Expanded list of predefined linkers from 5 to 22 for small molecule cyclization in macrocycle.py
• Expanded list of side-chain bridges for peptide cyclization from 4 to 21 of the most commonly reported in the literature
• Control spacers in macrocyclize.py via a CSV file of SMILES strings
• Improvements to macrocycle alignment reproducibility and performance in tug_align script and Ligand Alignment Panel
• Macrocycle sampling script can optionally output only macrocycle conformers
• Easily create cyclic peptides from sequence on the command line with peptide_cyclize.py script

De Novo Design

AutoDesigner – R-group Design

• Boost exploration of similar ligands with new AutoDesigner Similarity feature that scores output ideas based on similarity to a user-provided set of compounds
• Added exhaustive PathFinder enumeration of all routes of the starting ligand using all available building blocks for those routes
• Added recursive trimming of the final set of outputs to generate additional outputs
• Improved logging including an overview of the number of compounds generated at various stages of the workflow

AutoDesigner – Core Design

• Improved logging including an overview of the number of compounds generated at various stages of the workflow

Biologics Drug Discovery

• Predict protein properties with automated machine learning model building using protein descriptors: Leverage AutoQSAR analysis to train, validate, and apply AI/ML models for biologics properties prediction
• Predefined selection sets for quick access to TCR regions like CDRs, alpha/beta chains, and more

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Phonon-dependent dielectric properties reported in the Phonon DOS viewer
• Workflow action menu (WAM) for NMR calculations
• Support for phonon calculations with DFT-D3
• Improved cell relaxation protocol
• Schrödinger-compatible Quantum ESPRESSO releases available at Github
• Support for distributed phonon calculations
• Control over maximum number of retries after failure via config file (command line)
• Initial parameters and constraints preserved in the QM Convergence Monitor

KMC Charge Mobility

Product: MS Mobility

• Compute KMC Charge Mobility: Improved speed with robust QM convergence (command line)

Materials Informatics

Product: MS Informatics

• Formulation ML: Increased number of available steps for hyperparameter tuning
• Formulation ML: Option to replace hyperparameter tuning steps with training time
• Formulation ML: Visualization of atomic contributions from the feature importance analysis
• Machine Learning Property: Updates to existing models
• Machine Learning Property: Prediction of melting point for molecular solids
• Machine Learning Property: Prediction of non-aqueous solubility of molecules

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Automated CG Mapping: Speed up for mapping large molecules
• Automated CG Mapping: Particle types and the number of occurrences reported

Penetrant loading simulations

Product: Penetrant Loading (PL)

• Penetrant Loading: Differentiation between pre-existing water and added water

Reactivity

Product: MS Reactivity

• Nanoreactor: Option to set the width of the biasing potential
• Reaction Workflow: Anharmonic zero point energy (ZPE) added to Project Table
• Reaction Workflow: Support for enumeration on sites in rings
• Reaction Workflow: Option to automate the swap fragment with enumeration
• Reaction Workflow: Preview of reaction diagram at the setup

Microkinetics

Product: MS Microkinetics

• Microkinetic Modeling: Support for multistage MKM analysis
• Microkinetic Modeling: Support for zoom in on plots in the viewer panel
• Microkinetic Modeling: Increased default value for maximum integration time step

MS Maestro Builders and Tools

• Adsorption Enumeration: Support for selection of reactive atoms by atom indices
• Disordered System: Improved UI with reconfigured options for tabs and dialogs
• Disordered System: Support for keeping selected molecules rigid with tangled-chain option
• Meta Workflows: Support for radial distribution function analysis
• Nanoparticle: Option to include only molecules with center of mass inside the particle

Classical Mechanics

• Barrier Potential for MD: Option to remove barrier from input structures
• Droplet: Support for entering random seed in building a droplet
• Droplet: Support for randomized initial velocities
• Evaporation: Support for full control over which profiles to plot
• Evaporation: Support for applying barrier potentials
• Evaporation: Option to set evaporation zone based on the distance from COM of the substrate
• Evaporation: Improved loading speed for large input structures
• MD Multistage: Improved relaxation protocol for ladder polymers
• Refined default timestep for DPD particles
• Thermostat and barostat settings set automatically for atomistic and coarse-grained systems
• Stress Strain: Option to plot normal average stress
• Thermophysical Properties: Option to return *.ene files (command line)
• Trajectory Density Analysis: Output *.csv files

Quantum Mechanics

• Adsorption Energy: Option to select between kcal/mol and kJ/mol for energy units
• Adsorption Energy: All output entries incorporated in Project Table as subgroups
• Adsorption Energy: Robust detection algorithm for valid input adsorbates
• Adsorption Energy: Support for loading options from a Quantum ESPRESSO config file
• Optoelectronic Film Properties: Prediction of molecular refractive indices
• Optoelectronic Film Properties: Prediction of intersystem and reverse intersystem crossing rates
• Optoelectronic Film Properties: Improved loading protocols for large input structures

Education Content

Life Science

• New Tutorial: Protein pKa Prediction with Constant pH Molecular Dynamics
• Updated Tutorial: Glide WS Evaluation of HSP90 Ligands

Materials Science

• New Tutorial: Singlet-Triplet Intersystem Crossing Rate
• New Tutorial: Modeling the Formation and Decomposition of Nitrosamines
• New Tutorial: Atomic Layer Deposition
• New Tutorial: Elemental Enumeration
• New Quick Reference Sheet: Refractive Index
• Updated Tutorial: Introduction to Multistage Quantum Mechanical Workflows

Docs Content

• New documentation page to explore solutions for materials science applications and to identify the best fit for users’ interest
• Panel images shown in the help topic of each panel

LiveDesign

What’s new in 2024-4

• Biologics SAR Visualization: View, highlight, and analyze properties alongside sequence differences in the Sequence Viewer tool
• Ligand Designer
  • Upload multiple overlays in the Ligand Designer Configurations via the admin panel, and enable or disable the overlays during design sessions
  • Rename ligands after editing and using the “predict pose” functionality to track and manage iterative design changes
• R-group enumeration: Filter output products by computed properties
• LiveDesign Learning: View the LiveDesign Learning Dashboard within Landing Pages

  • *LiveDesign Learning is now called LiveDesign ML

• LiveReport Management
  • View row, column, and cell count for LiveReports in the LiveReport Picker
  • Set up a LiveReport as Read-Only or Hidden during creation in an updated Create LiveReport dialog
  • The following menu items have been consolidated into an “Edit LiveReport…” menu: Rename, Move to Folder, Make Read Only and Make Editable, Make Hidden and Make Visible
  • Admins can update Read-Only LiveReports to make them editable
  • Unhide a subset of compounds by clicking on a link in the LiveReport footer and selecting the compound IDs in a dialog
• Documentation
  • The ? button in LiveDesign now directs to online documentation as is done elsewhere in the Schrödinger platform. Users will be directed to log into their Schrödinger web account that will be verified with a code to their email; if they do not have a web account, they will need to sign up for one.
• Copy values from the Form spreadsheet, table, and ID widgets to the clipboard
• Search and filter for a column name in the Create MPO dialog when adding a constituent column from the LiveReport
• Click a link in a 3D cell for a 3D Generic Entity and Explicit Ligand Designer to view the 3D structure in Maestro
• Entities appear in a LiveReport more quickly after a reaction enumeration, R-group enumeration, file upload, Maestro upload, and LDClient upload
• LDClient’s API for retrieving FFC columns “get_freefrom_column_by_id” will now include an “updated_at” field containing a long corresponding to the timestamp that the FFC was last updated
• Landing Page: View recent published experimental data from the Compound’s Page

What’s Been Fixed

• Adding an entity to an Advanced Search, by searching for its ID, would show an unresponsive dialog, and now shows a dialog that accept an ID.
• Complex filters would not accept a pasted biologic sequence, and would fail to filter to that sequence, but now accept pasted biologic sequences.
• Creating a LiveReport from a template in the Landing Page would not open the newly created LiveReport, and now opens the LiveReport in a new browser tab.
• If an entity is imported to multiple projects, purging the entity from one of the projects will make it disappear from that project only. Only one file entry now appears in the Manage Files Dialog for a multi-entity import through CSV, ZIP, and FASTA.
• String type of entity relationship metadata is supported in DI by adding a DI mapping for relationship and relationship metadata.
• The column “Structure Class” has been renamed to “Entity Type” in the Data & Columns tree
• Pasting aromatic structures into the sketcher would flip chirality on structures containing a pyrrole, and now the chirality is maintained.
• When entering FFC date values via LDClient, users must now use the YYYY-MM-DD format. If the date is entered in an incorrect format, the system will return a 400 error with the message: ‘Date must be in YYYY-MM-DD format.’
• Forms kanban widgets would show a pin icon beside the kanban tile, and now pin icon does not appear in kanban widgets.
• Unpinning a row now works as expected.
• Model results with multiple values in a cell would show a different order of values if the LiveReport was duplicated, and now show the same order in the duplicated LiveReport as the origin LiveReport.
• The Guanidine group in Arginine incorrectly displayed a carbon with five bonds in the 3D visualizer, and now accurately represents the chemistry, showing the correct bonding structure for Arginine residues.
• Reordering of R-group scaffolds will work for newly added or deleted scaffold without page refresh in SAR analysis(R-group decomposition).
• The deleted docked poses will no longer reappear, ensuring a clean and organized workspace. Each new pose generated after clicking “predict pose” will be sequentially named, allowing for easy tracking (e.g., “docked_ligand_4” following the deletion of “docked_ligand_3”).
• Changing the model’s name via Admin panel will get correctly reflected in the Ligand Designer.
• Targets would remain visible in the 3D visualizer after unchecking the display checkbox and then selecting a different entity, and now the Target display checkbox remains unchecked and the Target is not visible.
• Copying a LiveReport from one project to another would grant the destination project ACLs to any model within the LiveReport, even if the Model’s Protocol did not provide access to the destination project. Now, the model column will be “dummified” and not visible in the destination project if the Protocol does not provide access to that project.
• Models with dependent parameterized models will not show an error when archived, and all of its dependent parameterized models will also get archived. A dialog box will appear stating the number of dependent parameterized models that will be archived.

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Create customizable histograms from numerical data that are automatically synchronized with selection or filtering in other charts, the Project Table, or Workspace
• Improved support for T-Cell Receptors with display of their annotations in the Structure Hierarchy

Force Field

• Full release of the OPLS5 polarizable force field for organic atoms for improved FEP+ and Desmond model accuracy

Workflows & Pipelining [KNIME Extensions]

In LiveDesign:

• Ability to use a single generic protocol regardless of model input columns
• LiveDesign connection node can take credentials from the session rather than storing them in the workflow
• Date type columns are supported as LiveDesign model input

Binding Site & Structure Analysis

SiteMap

• Enable compact mode for sites with volume larger than a cutoff
• New RNA mode for improved performance of SiteScore for RNA

Desmond Molecular Dynamics

• New Unbinding Kinetics workflow to gain insights into drug-target residence time and optimize in vivo efficacy, safety profiles, and ADMET (beta)
• Analyze halogen bonds in SID Panel
• View local strain energy in “Torsion” tab of SID Panel

Mixed Solvent MD (MxMD)

• Improved organization of output structures and data in prjzip file

Hit Identification & Virtual Screening

• Streamline visualization of hits in the Hit Analyzer by outputting VSDB per docking run by default
• Streamlined generation of WScore models with new WScore Quick Model Generation panel (beta)

Ligand Preparation

Hit Analysis

• Filter chemotypes by SMARTS in Hit Analyzer Panel

FEP+

• Improved management of pKa/tautomer/conformer ensembles on ABFEP systems with Groups tab
• Core-SMARTS selection no longer requires selecting explicit hydrogen atoms
• Improved user interface allows more intuitive column sorting
• Export to LiveDesign now includes additional fields
• Edge analysis now includes halogen protein-ligand interactions
• Guided access to open FEP+ Panel for analysis upon calculation completion via Workflow Action Menus (WAM) in Maestro

Protein FEP

• New lambda dynamics (λD) enhanced protein residue mutation FEP+ for identifying high quality protein variants (beta)
• Expanded OPLS5 support for “Protein FEP” and “Protein FEP for Ligand Selectivity” panels

Solubility FEP

• Expanded OPLS5 support for Solubility FEP simulations

FEP Protocol Builder

• Gain up to 35% speedup in calculations due to changed defaults in the FEP Protocol Builder panel

Biologics Drug Discovery

• Perform DNA/RNA nucleobase mutations using residue scanning on command line via mut-pred.py
• Analyze DNA/RNA interactions with proteins in the Protein Interaction Analysis panel
• Search the non-standard residues library and find the closest matching natural amino acid analog
• Automatically annotate and number T Cell Receptor (TCR) structures using IMGT or AHo schemes
• Use pose-viewer files as input for Protein Interaction Analysis

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Check for the number of irreducible k-points from the panel
• Upgrade to Quantum ESPRESSO 7.3.1
• Quicker assessment of electric field for faster phonon calculations
• Force and stress information reported in the project table
• Option for more diagonalization algorithms for GIPAW steps (command line)
• Option to set separate driver and subjob hosts for NEB calculations
• Solid State NMR Viewer: Improved UI for selecting elements

Transport Calculations via MD simulations

Product: MS Transport

• Diffusion: Support for non-orthorhombic systems as input

Materials Informatics  

Product: MS Informatics

• Formulation ML: Option to use Machine Learning Property predictions as descriptors
• Formulation ML: Option to use DeepAutoQSAR predictions as descriptors
• Machine Learning Property: Updates to existing models
• Machine Learning Property: Prediction of S1-T1 energy gap
• Machine Learning Property: Prediction of aqueous solubility
• Machine Learning Property: Output entries separated for each solvent

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Coarse-Grained Force Field Builder: Automated mapping for dissipative particle dynamics (DPD)
• Coarse-Grained Force Field Builder: Visualization of CG mapping in the workspace

Reactivity

Product: MS Reactivity

• Nanoreactor: Frames from MD trajectory added to list of products
• Nanoreactor: Support for multistate (e.g. singlet-triplet) reactions
• Nanoreactor: Number of loaded structures reported in the viewer
• Nanoreactor: Plot for reactants (red) shown with products (blue) in the viewer
• Nanoreactor: Reactant structures to be included as standard output
• Reaction Workflow: Support for AutoTS output as input

Microkinetics

Product: MS Microkinetics

• Microkinetic Modeling: Support for renaming of reactions and participating species
• Microkinetic Modeling: Automatic population of molecular weight for gas/solute species
• Microkinetic Modeling: Automatic assigning of collision factor based on reaction type

MS Maestro Builders and Tools

• Solvate System: Option to neutralize systems with built-in counterions

Classical Mechanics

• Barrier Potential for MD: Support for NPT ensemble
• Elastic Constants: Option to reset the viewer panel
• Meta Workflows: Support for trajectory-based free volume analysis
• Order Parameter: Option to compute acentric order parameter
• Polymer Crosslink: Option to use a barrier potential
• Polymer Chain Analysis: Support for molecules with less than 40 atoms

Quantum Mechanics

• Adsorption Energy: Option to constrain atomic positions for systems with PBC
• Optoelectronic Film Properties: Workflow solution encompassing transition dipole moment orientation and singlet excitation energy transfer (SEET) calculations

Education Content

Life Science

• New Tutorial: Introduction to MD Trajectory Analysis with Desmond
• New Tutorial: Re-scoring Docked Ligands with MM-GBSA
• Updated Tutorial: Understanding and Visualizing Target Flexibility
• Updated Tutorial: Approximating Protein Flexibility without Molecular Dynamics

Materials Science

• New Tutorial: Singlet Excitation Energy Transfer
• New Tutorial: FEP Solubility
• New Tutorial: Genetic Optimization
• New Tutorial: Adsorption of Panthenol on Skin with All-Atom Molecular Dynamics
• Updated Tutorial: Applying Barrier Potentials for Molecular Dynamics Simulations
• Updated Tutorial: Automated Dissipative Particle Dynamics (DPD) Parameterization
• Updated Tutorial: Design of Asymmetric Catalysts with Automated Reaction Workflow
• Updated Tutorial: Machine Learning Property Prediction
• Updated Tutorial: Crosslinking Polymers

LiveDesign

What’s new in 2024-3

• Uploads from Maestro to LiveDesign could fail if the LiveDesign project had more than 32,000 columns, and now complete successfully regardless of the number of columns
• LiveReports that contained columns with many values would show red error bars at the top of the LiveReport, and now no longer show the red error bars
• LiveReport tabs would disappear after logging out and logging in, and now correctly appear after logging back in
• New LiveDesign Learning module for rapid AI/ML molecular property predictions: Enables highly scalable, automated AI/ML pipelines for drug design
  • *LiveDesign Learning is now called LiveDesign ML
• Accelerated scaffold and R-group design with AutoDesigner Core Design: Automatically generate and optimize novel cores and R-group(s) simultaneously
• Delete Published Freeform column and Formula columns from the Data & Columns Tree
• Biologics:
  • Sequence-activity relationships in the Sequence Viewer:
    • Ability to add a quantitative column from the LR in the viewer
    • Correlate the changes in the residues and the activity data with the heatmap
  • There would only be one option when trying to import the Biologics data via csv and the option “Import As Single Entity for CSV” won’t show now.
  • Performance of structure hierarchy loading and item selection through hierarchy panel in the 3D Visualizer are improved.
  • Double-clicking an item in the hierarchy zooms to that selection in the 3D Visualizer workspace.
  • Set gap penalties in the sequence viewer to generate more useful alignments
• Landing Pages:
  • The Landing page now links to a specific URL and enable bookmarking the Landing Page in a browser
  • Download resources and files from the Landing Page Resource page
• Spreadsheet View:
  • A warning message alerting the user to expect decreased performance now appears on LiveReports that contain more than one million cells
  • Entity images no longer enlarge when hovering over the image, and can now be zoomed by clicking a magnifying glass button that appears to the right of the entity image
• The User details page in the Admin Panel now shows a warning that unlicensed usernames will not appear in dropdown lists throughout LiveDesign
• Models now support date and datetime returns
• Forms Matrix Widget now render larger editing areas for Freeform column cells when the cells are small

What’s Been Fixed

• LiveReports would show red error bars when multiple input values to a parameterized model changed simultaneously in the spreadsheet, and now the LiveReport loads correctly
• Popping out a model column’s cell that contained and image would open two tabs in the browser (one tab with the image, and one blank tab), and now only opens a tab with the image
• LiveReports would occasionally lose their filters, and the filter panel would appear blank, but no longer lose their filters
• Changing a user’s role within a Single Sign-on Identity Provider would not update the user’s role within LiveDesign when they logged out and logged back in, and now the role changes are correctly used after the user logs out of LiveDesign and logs back in
• Changes to parameterized model in the Admin Panel (e.g., the Title or Folder) would not save after clicking the Save button, and now correctly save and update the parameterized model
• Changes to a “set fixed” protocol parameter get passed along to the dependent model or parameterized model without breaking them.
• The Formula Substructure Search function incorrectly reported the count of substructure matches as 1, even if there were multiple matches, and now correctly reports the total number of substructure matches
• Adding a new project with an identical name to an archived project provided a cryptic error message, and now provides a clear message instructing the user to choose a different name
• When many LiveReports were open, the active LiveReport tab would disappear when left-side panels were opened, and now the active LiveRepot tab remains visible
• Newly created models would not inherit the Recalculate Model option defined in the protocol, and would default to the “Automatically” option, and now the models correctly inherit the option defined in the protocol
• Parameterized models that have had their columns renamed in the Admin Panel would show the old, original column names when that model was added to LiveReports, and now correctly show the updated column name
• The user interfaces of the Filters panel and Advanced Search panel have been unified
• Changing the column widths within the LiveReport picker caused the column header to misalign with the column contents, and now the header remains aligned
• The prefix (Global) would appear repeatedly for templates in the Global project that were updated and overwritten, and now templates in the Global project only show a single (Global) prefix after they are updated and overwritten
• Maestro would not import 3D results from LiveDesign when the 3D column title was renamed, and now correctly imports all 3D data regardless of the column title
• LiveDesign would occasionally freeze due to a database lock, and now no longer will freeze
• Opening a model attachment from the main spreadsheet (e.g., a LID from a Glide model) would fail to show the image, and now correctly shows the image
• Filtering out a frozen row would show flashing squares in the first row in the main spreadsheet, and now correctly shows that row’s data
• The Project Picker would appear after a five-second delay when there are a large number of projects to show, and now the Project Picker appears instantly
• The sequence viewer would occasionally show incorrect colors and tooltips for non-natural amino acids, and now shows the correct information
• Hovering over a residue in the sequence viewer would cause the viewer to scroll to the top, and now the scroll position remains does not change
• Plot tooltips could not be dragged and moved after pinning to the screen, and now can be dragged to a new position after pinning
• Model results would occasionally appear as Failed in the LiveReport, when in fact the model ran successfully, and now model results correctly show results in the LiveReport

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Dynamically display measurements based on selected atoms in the Status Bar
• Copy fragments from existing molecules in the 3D Workspace and paste them onto selected atom(s) in another molecule
• Export movies from the Trajectory Viewer with the Workspace resolution
• Search in the Entry List using regular expressions for greater precision. Simultaneously search for multiple structures
• Aligned pharmacophore label font with Maestro font preferences
• Display T-cell receptor annotations in the Structure Hierarchy
• Automatic synchronization of data point selection in scatter plots with Project Table selections and/or Workspace inclusion
• Display data from different groups in a single scatter plot

Force Field

• New OPLS5 Force Field (beta): Significant improvement in the accuracy of cation-pi and ionic group interactions via the addition of limited polarizability in relative binding-FEP+ and Desmond. Available as a new option alongside the default OPLS4

Workflows & Pipelining [KNIME Extensions]

• Supports the latest version of KNIME (v5.2)
• The Chemistry external tool node supports a new FEP+ column type that points to fmp files read by the FEP+ reader node

Binding Site & Structure Analysis

SiteMap

• More accurate identification of RNA binding sites with 89% of RNA sites in HARIBOSS set now identified as the top-ranked binding site by SiteMap, up from 69% previously (beta)
• New SiteMap parameters to separate large pockets that are bleeding into one another or across the protein surface and identify smaller distinct sites (command line only)

Mixed Solvent MD (MxMD)

• Support for membrane systems

Hit Identification & Virtual Screening

Ligand Preparation

Active Learning Applications

• Enhanced diversity selection in AL-Glide through consideration of up to 3x more compounds by horizontal scaling of diversity selection
• Significantly improved LigandML prediction throughput in AL-Glide through use of ZMQ (command line only) (beta)
• Much faster file uploading to the DriverNode in AL-Glide (command line only) (beta)

Ligand Docking

• Improved pose-prediction and enrichment when docking small molecules into RNA receptors with Glide (beta)

Lead Optimization

FEP+

• Support setting up Positional Restraints in RB-FEP via FEP+ panel
• Ability to use OPLS5 for Increased RB-FEP Accuracy
• Improved Trajectory Management allowing trajectories from multiple edges in PT

Protein FEP

• Support of Multi-Site Mutations for Thermostability prediction

Constant pH Simulations

• Support of Lys pKa Calculations with panel support

Solubility FEP

• Improved Trajectory Visualization
• Link to Best Practices document
• Support of Force Field Builder from Web Service

FEP Protocol Builder

• Use FEP Protocol Builder to quickly identify FEP+ model parameters that optimize FEP+ accuracy using an automated machine learning-driven workflow
  • Free researcher time by letting the FEP Protocol Builder explore parameter space to identify and visualize optimal parameters for FEP+ model performance
  • Find FEP models for challenging systems through efficient exploration of parameter space
  • Proceed with confidence to use FEP+ prospectively in your program
  • Interface to set up FEP protocol optimization calculations with automated assignment of ligands into test/training sets
  • Interface to analyze influence of parameters on FEP model performance and compare protocol performance via FEP+ correlation plots

Quantum Mechanics

• Perform wave function stability analysis in Jaguar
• Generate NMR chemical shifts and spectra of 19F isotope with Jaguar Spectroscopy
• Set multiplicity automatically (multip=2) if an odd number of electrons are found in Jaguar
• Search for atropisomers using the new rotation_barriers.py script (command line only)
• More robust and performant E-sol workflow suitable for LiveDesign and command line execution 
• Modify level of theory and basis sets of multiple entries with a right mouse click

Medical Chemistry Design

Ligand Designer

• New Ring Swapping workflow to optimize lead compounds by exploring alternative ring scaffolds (beta)

Biologics Drug Discovery

• Added 430 new non-natural amino acids to the library for use in peptide design
• Interface improvements to speed analysis of protein mutation results produced by residue scanning
• Analyze structural ensembles such as PIPER docking results and MD trajectories  with Protein-protein interaction analysis panel (open beta)
• New option to specify one of five numbering schemes, Chothia, Kabat, IMGT, Enhanced Chothia or AHo, when performing antibody structure alignment using the align_antibody.py script

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Input for magnetization from structure data (command line)
• Results viewer for solid state NMR spectra
• NEB Convergence Monitor: Display of relative / activation energies
• Automatic shift of K-point grids for improved convergence
• Option to compute and visualize potential surfaces in the workspace
• Phonon Density of States Viewer: Support for dielectric constant
• Speed-up of NEB calculations with smart management of wave function data

KMC Charge Mobility

Product: MS Mobility

• Compute KMC Charge Mobility: Charge transfer computed based on center-of-mass distances

Materials Informatics  

Product: MS Informatics

• Formulation ML: Support for input data with missing component names / SMILES
• Formulation ML: Support for Set2Set and graph-based models and descriptors added
• Formulation ML: Option to remove highly-correlated descriptors (command line)
• Formulation ML: Option to control the training set size
• Formulation ML: Support for classification mode
• Formulation ML: Feature-importance analysis based on Shapley additive explanations (SHAP)
• Machine Learning Property: Improvements in prediction models available for download
• Machine Learning Property: Prediction of oxidation and reduction potentials
• MD Descriptors: Support for formulations-focused descriptors

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Coarse-Grained Force Field Builder: Automatically map atomistic systems to Martini particles (command line)
• Coarse-Grained Force Field Builder: Fit Martini parameters (command line)

Reactivity

Product: MS Reactivity

• Nanoreactor: Improved default settings
• Nanoreactor: Speed-up of xTB frequency calculations
• Nanoreactor: Improved deduplication algorithm for products
• Nanoreactor: Improved parallelization algorithm
• Nanoreactor: Option to remove high-energy products
• Nanoreactor: xTB free energy used to rank-order products
• Auto Reaction Workflow: Prevention of excessive equilibrium constant calculations from permutations

Microkinetics

Product: MS Microkinetics

• Microkinetic Modeling: Support for the use of analytical Jacobian
• Microkinetic Modeling: Option to specify collision factor
• Microkinetic Modeling: Results returned for cases that did not reach a steady state
• Microkinetic Modeling: Option to list chemical equations from the input reaction network

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Reaction-template based solution for dynamic simulations of materials systems near battery electrodes

MS Maestro Builders and Tools

• Density Profile: Visualization of density isosurfaces
• Complex Builders: Option to clean up geometry using xTB
• Semicrystalline Polymer: Support for polyvinyl alcohol (PVA)
• Solvate System: Protocol to manage output with more than 2M atoms
• Structured Liquid: Protocol to manage output with more than 2M atoms
• Structured Liquid: Improved and expanded built-in lipid library

Classical Mechanics

• Thermal Conductivity: Solution to predict thermal conductivity of solids

Quantum Mechanics

• Adsorption Enumeration: Improved algorithm to define surface atoms
• Adsorption Enumeration: Heavy-atom filter for reactive atoms
• Amorphous NMR: Isosurface data available from QM calculations

Education Content

Life Science

• New Tutorial: Ligand Binding Pose Prediction for FEP+ using Core-Constrained Docking (NEW)
• New Tutorial: Ligand-Based Virtual Screening Using Phase (large-scale rework from the ground up)

Materials Science

• New Tutorial: NMR Spectra Prediction
• New Tutorial: Thermal Conductivity
• New Tutorial: Solid Electrolyte Interphase Calculations
• New Tutorial: Building a Semicrystalline Polymer
• Updated Tutorial: Machine Learning for Formulations
• Updated Tutorial: Update tutorials for switch to RDKit (affects multiple tutorials)

LiveDesign

What’s New in 2024-2

• Biologics Support
  • Upload peptides, monoclonal antibodies, bispecific antibodies, Fab, Fab2, Fv, DNA, and RNA
  • Biologics automatically get broken down into their component chains and can be visualized in composite rows
  • View and align sequences in a sequence viewer
  • Upload experimental data and metadata
  • View 3D model results and apply styling
  • View antibody hierarchy in 3D visualizer and select and style at full biologic, domain (ex: VH, CH1), subdomain (ex: HCDR3), or residue level
  • Full support within Models, MPOs, Formulas, Freeform columns, Forms, Tile View, Filters, and Search
  • Search and Filter for Biologics based on the properties of their chains
• Updated User Management in the Admin Panel
  • See and update all Users’ ACL and details on single page
  • Quickly add and remove multiple users at once
  • Bulk update user roles, projects, license status
  • Create a project and add users, groups, admins to the project on single page
  • Project and Group details pages give clearer statistics on users and access control flow
  • Choose to send or resend a welcome email on updates
  • Sync users between LiveDesign and externally hosted, read-only LDAP, to pre-populate users before their first login
• One-click to view 3D model results in Maestro: Click a link in a 3D model cell to automatically open Maestro and view the result. Note that this only works in Windows, using Maestro version 24-2; Mac and Linux support are forthcoming in Maestro’s 24-3 release
• Structure Groupings for the 3D Visualizer
  • Group any number of 3D outputs in a single structure group, beyond the historic Ligand + Protein combination
  • Add custom group titles to change the displayed column title
  • View multiple ligand poses or protein poses in the 3D visualizer content panel
• Control Display styles in Ligand Designer
  • Style selected atoms, resides, and chains from a new toolbar within the 3D canvas in Ligand Designer
  • Apply custom styling to Proteins and Ligands within a Ligand Designer session
  • Use 3D tools within Ligand Designer, such as export, zoom, and screenshot
• Complex Filters: Combine filter conditions using AND or OR logical operators
• Published Limited Assay Columns: Publish limited assay columns so they appear in the Data & Columns tree, and are available for use in published column-as-parameter models, MPOs, and published formulas
• Pinned Rows: Click a button on a row or a Tile to “pin” the compound to the top of the LiveReport
• UX Improvements
  • Forms
    • Toggle the number of tiles to show in each row in a Kanban widget
    • Freeform column cells now render larger editing areas in the Matrix Widget when the cells are small
  • Plots
    • Plot can’t be created or edited in read only LRs
    • Delete plots directly from the visualize panel, without opening them first
    • Search for columns in plot axis selection dropdowns
  • Spreadsheet interactions
    • Freeze multiple columns at once via the column menu
    • Double-click on a Freeform column cell to edit its value
    • The Run button for click-to-run models is now displayed as a solid color
    • Right-click on a LiveReport tab to reveal the LiveReport menu
  • 3D Visualizer
    • Downloaded files from the 3D visualizer now show the same labels in Desktop PyMOL instead of hashed values
    • Binding Site Interaction Map is turned off by default when opening a Ligand Designer session
  • Miscellaneous
    • The login page now allows submitting either Single sign-on or username + password credentials
    • Export the Tile View configuration to PPTX using LDClient
    • Archive a model without fixing errors in the model settings
    • The Job Manager gadget table now resizes as the tool is resized
    • Click Help icons in the Create Freeform Column dialog, Create Formula column dialog, and the Define New
    • Multi-Parameter Optimization dialogs to navigate directly to the user manual
    • Click an icon within the Data & Columns Tree LiveReport tab to scroll to the column in the LiveReport
    • Drag and add multiple scaffolds to the R-group enumeration scaffold sketcher
• TaskEngine workers now scale up when the number of submitted jobs increases
• The Schrodinger Suite python method “from schrodinger.structure import SDReader” has been deprecated, and scripts should instead call “from schrodinger.structure import StructureReader”

What’s Been Fixed

• The Landing Page Overview would occasionally fail to show the most recently added compounds, and now correctly shows them
• Columns that are added to LiveDesign via the Data Integrator are now set to the correct datatype
• LiveReports no longer show duplicate rows for a Real and a Virtual after uploading experimental data via ACAS
• LiveDesign now correctly opens the most recently opened Project and LiveReport after logging in
• Users can now log out of LiveDesign when Single Sign-On is enabled
• Freeform column picklist options order would previously change, and is now maintained according to the configuration set within the Edit Freeform Column dialog
• Duplicating a LiveReport with many unpublished assay data points is now up to 6x faster (duplicating LiveReports with fewer unpublished assay data points will experience less of a speed up)
• Pasting specific LiveReport URL into the browser would occasionally redirect to the Project Picker, and now correctly opens the LiveReport
• Security
  • CVE-2023-44487 has been patched
  • Sessions cookies are now marked Secure
• Admin Panel
  • Uploading a file in the Admin Panel now works correctly when the filename is identical to the file that is being replaced
  • The Last Modified Date shown in the Admin Panel’s Protocol page and Protocol List page now correctly updates for all changes to the Protocol
  • The “Last Login” date field within the Admin Panel’s User page now correctly updates
  • Parameterized models could not be modified in the Admin Panel after creation, and now can be modified (e.g., change the title or folder)
• File Exports
  • Enhanced stereo labels now show in all images in PowerPoint exports
  • Exporting Tile View to PowerPoint now correctly warns the user when attempting to show more than 8 compounds per slide
  • Exporting LiveReports to SDF would sometimes fail if the LiveReport contained click-to-run model columns, and now no longer fails
• Forms
  • Tiles now render correctly in Tile View widgets, when the Tile View widget is in the same container as another widget
  • Tooltips in Tile View would previously get frozen after displaying R-group decomposition results, and how correctly show data for each cell
  • Tile view tooltips now render correctly-sized R-groups when hovering over a R-group decomposition cell
  • The Forms Entity Image widget now correctly shows the ID of the entity
  • Forms drilldown from a row-per-compound widget to a row-per-pose widget now correctly shows the poses only for the selected compound(s)
  • The Forms Matrix widget now shows the entity image for Generic Entities
• LDClient
  • A ‘parent_row_key’ has been added to the LDClient RowInfo object within LiveReportResultsMetadata, which identifies which rows are child composite rows in the LiveReport
  • LDClient ldclient.LDClient.refresh_db_constants method and the AboutInfo remaining_read_only_licenses_count field have been deprecated and removed
  • LDClient now correctly returns a LiveReport’s filters, when the filters include a substructure query
  • LDClient’s ModelTemplateVarType enum now includes LIST_INPUT and RDKIT_MOL
  • Scripts calling LDClient occasionally needed to execute a LiveReport, and include a manually programmed sleep to get results. LDClient now includes a method mutate_then_wait, which allows code to wait on actions to be completed before continuing (such as adding rows to a LiveReport)
• Ligand Designer
  • Ligand name shows up correctly in Ligand Designer, when the LiveReport is in row-per-pose mode
  • Grid files can now be changed for existing Ligand Designer configurations in the Admin Panel
• Maestro Export
  • LiveReport exports from LiveDesign to Maestro now work correctly when two Real compounds are linked to the same Virtual compound
  • Maestro exports to LiveDesign with published data are now faster
• Matched Molecular Pairs
  • Previously calculated Matched Molecular Pair analyses have been deleted due to a backwards-incompatible Python library upgrade, and must be re-run
  • The Matched Molecular Pairs tool now shows an error message when large LiveReports fail to complete the matched pairs computation
• Spreadsheet Interactions
  • Searching by substructure in the active LiveReport will now deselect existing row selections, and select the matching substructures
  • Compound orientations in the sketcher are now saved when adding the compound to a LiveReport, using a scaffold in R-group decompositions, using a scaffold for compound alignment, and using compounds in enumeration
  • The row-per-model toggle is no longer obscured when the visualizer panel is open
  • Searching a LiveReport via the magnifying glass now correctly navigates to the first matching string
  • Calculated properties that appear below the sketcher now truncate long column names to avoid an overlap with the calculated value
  • Attempting to recalculate an archived model would show flashing cells, as if the calculation has been started (despite no calculating being started), and will now show an error message
  • Searching for metadata within assay columns’ Edit Tooltip Content now correctly filters content that does not match the query
  • Copy and Paste coloring rules for R-group decomposition columns
  • Copying a compound into the sketcher via the row menu’s “Use in → Design/Search Sketcher” option will now correctly overwrite any compound within the sketcher
  • Importing a compound multiple times to the sketcher using its ID will now correctly show the compound’s structure
• Plots
  • Box plots now show a border around selected outlier data points to make them more noticable
  • Scatter plot tooltips now show assay datapoint operators, such as ‘greater than’ and ‘less than’

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Improved usability for several Project Table dialogs including Change Property, Substructure Count, Add Property, Add Sequential Index Property, Add Standard Molecular Property, Redo Calculation, and Total Surface Area
• Improved usability of the Find Toolbar by adding a close button and “Search in Progress” indication

Workflows & Pipelining [KNIME Extensions]

• Stabilized version of the KNIME generic LiveDesign protocols
• New node for pKa prediction using Epik 7
• Added support for AB-FEP files to FEP+ reader node

Target Validation & Structure Enablement

Protein Preparation

• Improved accuracy of ligand ionization/tautomeric state predictions in the Protein Preparation Workflow using ML-enabled Epik by default
• Ability to optionally provide sequence information via FASTA file when filling in missing loops

Multiple Sequence Viewer/Editor

• Ability to export sequences and annotations to seqD file

Binding Site & Structure Analysis

Desmond Molecular Dynamics

• Added Radial Distribution Function (RDF) analyzer in Trajectory Plots

Hit Identification & Virtual Screening

Ligand Preparation

Empirical and QM-based pKa Prediction

• Improved accuracy in empirical corrections for Macro-pKa from a new ML-based algorithm used by default

Lead Optimization

FEP+

• Improved functionality of FEP+ Panel-managed trajectories can now be moved out of the FEP+ entry group, to retain it in the project table

Protein FEP

• Mutation generation will now ignore water molecules for sidechain placement

Solubility FEP

• Ability to compute hydration free energies from Solubility FEP with useful blood brain barrier penetration correlation: Hydration-only mode is now available from Advanced Options of the Solubility FEP panel

Quantum Mechanics

• Employ different basis sets by atom in Jaguar Transition Search
• Predict and view NMR spectra based on DFT chemical shifts and spin-spin couplings
• Added support for analytic basis sets with high angular momenta including cc-pvXz and def2 basis sets up to QZ
• Added support for composite 3c-functionals: HF-3c, PBEh-3c, HSE-3c, B97-3c, r2SCAN-3c, and wB97X-3c

Biologics Drug Discovery

• Improved accuracy in antibody modeling with new curated antibody database that now excludes redundant and/or poor-quality PDB structures
• Option to export all 1000 unclustered raw poses from PIPER protein docking
• Report the % humanness of the Heavy and Light chain on the grafted model in Antibody humanization by CDR grafting
• Export aggregation profile images in png format
• Report detailed patch characteristics in Protein Patch calculations
• Easily perform detailed analysis of residue scanning results with new csv file containing mutant descriptions and energies

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Convergence monitor for the nudged elastic band (NEB) calculations
• Workflow for computing dielectric constant (command line)
• Support for parallel computation of Phonon calculations (command line)
• Option to display discrete frequencies from dynamical matrix for phonon DOS
• Support for phonon calculations with Hubbard U potentials for LDA+U
• Support for mean square displacement analysis over an existing AIMD trajectory

Materials Informatics

Product: MS Informatics

• DeepAutoQSAR: Access from the Task menu under Materials Informatics
• Formulation ML: Machine-learning-based property predictions using chemical formulations
• Machine Learning Property: Improved machine learning models
• MD Descriptors: Bond, angle, torsion, and vdW energies computed as descriptors
• MD Descriptors: Improved efficiency with the MD simulation protocol

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• CG FF Builder: Implicit charge assessment by dielectric constant
• Automated DPD Mapping: Support for multiple ionization states (command line)
• Automated DPD Mapping: Support for pre-defined patterns for use in mapping (command line)
• Support for including CGFF file (*.json) information into other CGFF files

Reactivity

Product: MS Reactivity

• Schrödinger Nanoreactor: Chemical reaction discovery and analysis module based on AIMD and semiempirical QM (xTB) methods
• Auto Reaction Workflow: Improved speed in calculating custom rates and K_eq

Microkinetics

Product: MS Microkinetics

• Workflow module for microkinetic modeling of chemical reaction rates

MS Maestro Builders and Tools

• Complex Enumeration: Support for the use of two ligand libraries as input
• Complex Enumeration: Option to specify the number of unique ligands
• Move Selected Atoms: Workspace tool to rotate/translate selected atoms

Classical Mechanics

• Polymer Crosslink: Option to block formation of specific chemical structures
• Molecular Deposition: UI update with improved control of adsorbate setup and simulation protocols

Quantum Mechanics

• TST Rate: Jobs launched to queue

Education Content

Life Science

• New Tutorial: Ligand-based Screening for Ultra-Large Libraries with Quick Shape and the Hit Analyzer
• New Tutorial: Designing Out Common ADMET Liabilities using Consensus IFD-MD
• New Tutorial: Introduction to MD Simulations with Desmond
• Updated Tutorial: Structure-Based Virtual Screening using Glide

Materials Science

• New Tutorial: Microkinetic Modeling
• New Tutorial: Machine Learning for Formulations
• New Tutorial: Nanoreactor
• New Tutorial: Modeling Receptor Binding in an Olfactory Protein
• New Tutorial: Building a Coarse-Grained Skin Model using Martini Force Field
• Updated Tutorial: Activation Energies for Reactivity in Solids and on Surfaces
• Updated Tutorial: Molecular Deposition

LiveDesign

What’s New in 2024-1

• Limit Unrestricted Project Data Visibility: Configure a project so that compounds, data, and models from unrestricted projects and the Global project are not accessible within that project
• Export Tile View to PowerPoint:
  • Fields defined for the Tile are automatically selected for export
  • The order of fields in the Tile match the order generated in the exported PPTX
  • Choose the number of Tiles (1-8) that should appear on each slide
  • The Compound Structure row with SMILES content is no longer included
• Forms Improvements
  • Change the styling of Matrix Widget text labels cells with font styling, background colors, and font alignment
  • The Matrix widget will now slightly resize automatically to adapt to different screen resolutions (down to minimum column width of 75 pixels, and a maximum width of 210 pixels)
  • Boolean Freeform column cells now render smaller, more usable buttons in the Matrix Widget
• Landing Page Improvements
  • Centralize project collateral by adding hyperlinks to key presentations, notes, or papers on a new Project Resources page
  • Tag compounds as Favorites within the Landing Page’s Compound page. Favorited Compounds are visible on Project Overview page
• Configure Assay Tooltips: Configure what metadata appears within assay tooltips on a per-assay, per-column, or per-LiveReport basis
  • Define pattern matching rules within the Admin Panel for entire assays or specific endpoints to control which metadata shown among all Projects
  • Define LiveReport-specific metadata visibility through the Assay’s column menu
  • Configure what metadata appears in assay tooltip through LDClient
• 3D Visualizer Improvements
  • Unit cell box can be rendered in the 3D workspace
  • Changing dihedral angle button is moved from the ‘More’ dropdown to the Ligand Designer Edit main tool bar
  • Clicking “X” on 3D window exits Ligand Designer, instead of hiding the panel, just like clicking the “Done Editing” button
  • The pose name that appears in Ligand Designer is the name of the reference file uploaded in ligand designer configuration for explicit Ligand Designer models.
• Composite Row Improvements
  • Create a new entity or clone an existing entity in Entity Groupings Tool
  • Drag and drop an entity (or a group of entities) off the Entity Groupings Tool table to remove the entries from a relationship, or drag and drop entries within the table from one location to another
  • Create entity relationship metadata columns. List entity relationship metadata columns in the Data & Columns tree, and add entity relationship metadata columns to a LiveReport and view the metadata values in the LiveReport
  • Add Composite Metadata Columns in the Entity Groupings Tool to edit the metadata for new entities
• The Tasks page within the Admin Panel now permits killing an unlimited number of tasks
• Retrieve assay metadata from the LDClient python API
• Generic Entity experiment imports now show a notification when the import is complete, with a link to the import summary
• User-initiated operations (e.g., Filtering and R-group decompositions) are now prioritized more highly than background activities, such as auto-updating advanced searches, to reduce latency

What’s been fixed

• Generic Entities
  • A warning message is shown when importing a Generic Entity experiment file with duplicate column headers
  • Importing generic entities through LDClient would fail if the request attempted to update the entity with a specific file, and now importing succeeds
  • Experiments imported for Generic Entities appear the Experimental Assays folder in the data and columns tree
  • The Entity Groupings tool can now quickly load tens of thousands of rows and operations within the tool are more performant
  • Generic entity metadata tooltips now correctly appear in Tile View
  • Tile View now correctly shows file icons for Generic Entities
  • Importing experimental results for Generic Entities previously showed an unnecessary error message dialog, even when importing experimental results was successful, and now no longer shows the error dialog
  • Using the “Show as text” option in the Entity column menu would show distorted icons for Generic Entities, and now correctly show empty values
  • Exporting LiveReports to CSV and XLS previously failed to export Generic Entities that had values for their Lot Properties, and now correctly exports those entities and values
  • Clicking on the Manage Files button within the Import panel would open the File Import dialog, and now opens the Manage Files dialog
  • Entity bank and relationship table are synced up with the current LR when switching LRs.
• Models
  • Taskengine would occasionally fail to find the Schrodinger Suite when running models, and now correctly finds and mounts the Schrodinger Suite
  • PyMOL session files (.pse) generated by models failed to be truncated around the ligand, are now successfully truncated to reduce their file size and speed up loading times in the 3D visualizer
  • Long-running model tasks results would occasionally fail to get imported to LiveDesign due to network connectivity issues, and now successfully import
  • LiveDesign would incorrectly declare some model tasks as “Failed” if they remained in a TaskEngine queue in the Submitted status too long, and now LiveDesign correctly runs the tasks and imports the results
  • 3D models columns would occasionally return a blank cell, and now always show either “3D not available”, “Failed” or the Methane icon
  • Pending cells in the LiveReport would remain flashing even if the task was killed in the Admin Panel, and now the cells correctly indicate that the task was killed
  • Using the ${LIVEDESIGN_URL} macro in a model would fail to connect to LiveDesign, and now successfully connects to LiveDesign
• 3D Visualizer
  • The 3D Visualizer’s Reset Custom Styles button failed to reset some styling options applied to proteins, and now correctly resets all styling, including for selected atoms
  • Styles applied in the 3D visualizer are now visible after switching the 3D visualizer to Popout Mode
  • Ligand Designer sessions no longer show a message that zero docking jobs are queued when the docking queue is empty
  • Not all color changes applied to ligands and proteins within the 3D visualizer would be saved, and now color changes are correctly saved
• Plots
  • The Configure Tooltips dialog for Plots would incorrectly show columns in the Displayed Fields section of the dialog after canceling changes to the tooltip, and now correctly shows columns within the Displayed Fields section
  • Color segment orders within Histogram plots now show colors in the following order: Categorical coloring rules follow the order of the defined rules within the Coloring Rules dialog. Gradient and numerical coloring rules follow the order of the bins is based on the numeric sort order
  • Long entity IDs would previously overflow within plot tooltips, and now wrap within the plot’s tooltip
  • Plots with lots of data can export SVGs in Firefox
  • Box plots now show a border around outlier data points
  • Selecting a box within the box plot would hide the median line, and now the median line is always shown regardless of selection
  • The dialog that configures plot tooltips now correctly shows the columns in the tooltip within the Displayed Fields section
  • The jitter banner appears in front of the legend and not overlapping with each other
• Filters
  • Dropdown lists previously listed options that were visible in a LiveReport after a Filter was applied, and now list all options for the LiveReport (including any options that have been filtered out)
  • Numeric filters now show a precision of up to 1e-9
• The LiveReport footer’s selection navigation interface now shows the compound’s preferred ID
• The LiveReport footer previously read “Entities displayed”, even when there were no Generic Entities within the LiveReport, and now reads “Compounds displayed”
• Boolean Freeform columns now render the checkmark and X icon correctly in Firefox
• Substructure and Similarity searching previously used LiveDesign’s absolute maximum number of search results to return, and now correctly use the system-configurable default value for the maximum number of results to return
• LiveReports that contain columns from a Reaction Enumeration or R-group Enumeration now open more quickly
• Compounds would occasionally disappear temporarily when added to a large LiveReports, and now correctly remain visible in the LiveReport
• LiveReports with auto-updating advanced searches no longer attempt to update the report more times than necessary, which conflicted with user activities and slowed them (e.g., R-group decompositions and Filters)
• Dropdown options were not fully visible within the Parameterized Model dialog, when the model options were defined with a picklist, and now the dropdown options are correctly displayed
• The Matched Molecular Pair tool now functions correctly while toggling between multiple compound selections in the LiveReport and using the MMP tool
• Usernames are no longer case sensitive, and usernames with a different case are deduplicated
• LDClient now successfully exports a LiveReport to CSV when a token is used for authentication
• Kanban widgets now correctly show picklist Freeform column values that have been applied to existing compounds, but that have been removed from the Freeform column configuration and aren’t available to apply to new compounds
• Selecting a composite row parent and recalculating a model would trigger a recalculation for all children, and now only recalculates the model for the selected parent
• Matrix widgets no longer appear broken after duplicating a LiveReport with a Matrix widget that contains unpublished columns
• Compound orientations in the sketcher are now saved when adding the compound to a LiveReport, using a scaffold in R-group decompositions, using a scaffold for compound alignment, and using compounds in enumeration
• The date range filter for recently added compounds in Landing Pages now renders correctly
• Ligand Designer sessions no longer get stuck in a Loading state
• Column-as-parameter models now provide correctly formatted CSV files when the input column is a 3D column that is tagged as an “Other” type (as opposed to a “Ligand” or “Protein” type), and the lists each input as a separate row
• Selected compounds are highlighted in green in Heatmap
• Model Task pages in the Admin Panel now report if a prediction column is missing from the task output
• The Project Picker would appear after a five-second delay when there are a large number of projects to show, and now the Project Picker appears instantly
• SDF Exports were limited to 20mb, and now are limited to 4gb
• LiveDesign would occasionally freeze due to a database lock, and now no longer will freeze

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Improved functionality and enhanced usability in the new embedded Workspace Sequence Viewer [2023-4]
• Improved Scatter Plot capabilities: An updated charting tool provides a more intuitive interface, interactive features for data exploration, and extensive customization options for generating scatter plots [2023-4]
• New Lasso Selection: Draw a freeform selection path with superior precision around specific atoms or regions compared to Marquee Selection [2023-4]
• New 3D Builder behavior preference to automatically minimize newly added fragments [2023-4]
• Redesigned ‘Find Toolbar’ boasts an improved user interface with new functionalities such as sequence search and enhanced “Search by SMARTS” with access to the Sketcher [2023-4]
• Added support for Nonstandard Amino Acids in the 3D Builder [2023-4]
• Improved user interface for several Project Table dialogs [2023-4]:
  • Combine Properties
  • Copy Property
  • Delete Properties
  • Clear Values
• Added menu option to move selected entries to the top or end of their current group [2023-4]
• Enhanced surface visuals through texture mapping, utilizing per-vertex texture coordinates to enrich detail and color vibrancy [2023-4]
• mmCIF files (.cif) are now treated the same way as PDB files (.pdb) upon import into Maestro, with atoms automatically colored by element for improved visualization [2023-4]

Force Field

• FFBuilder now uses the QRNN-TB neural network potential as its default reference method. Typical FFBuilder jobs run 3-5X faster [2023-4]

Workflows & Pipelining [KNIME Extensions]

• LiveDesign connection node supports Single Sign-On and reconnection to hosts running different LiveDesign versions [2023-4]
• LiveDesign connection node can be connected to the Upload as LiveDesign node [2023-4]
• LiveDesign settings are stored for several hosts as profiles in KNIME preferences panel [2023-4]

Target Validation & Structure Enablement

AlphaFold Download / Process

• Added support for processing AlphaFold2 models and PAE files created through ColabFold [2023-4]

Multiple Sequence Viewer/Editor

• Full release of ‘Align by Family’ panel (removed beta label) [2023-4]
• Added T-Cell receptors as newest protein family recognized and property annotated with sequence features [2023-4]
• Support for family aware alignment of T-Cell Receptor sequences to enable downstream applications like homology modeling [2023-4]

Binding Site & Structure Analysis

Desmond Molecular Dynamics

• Radial Distribution Function (RDF) Panel can now ‘Group’ sites by monomers [2023-4]

Mixed Solvent MD (MxMD)

• Added support for fragment-size probes [2023-4]

Hit Identification & Virtual Screening

Ligand Preparation

Empirical and QM-based pKa Prediction

• Improved Lewis structure canonicalization in Epik [2023-4]

Lead Optimization

Ligand alignment

Improved performance of macrocycle alignment for cis- and trans-bond containing macrocycles [2023-4]

FEP+

• Improved analysis of multiple physical properties in FEP+ panel [2023-4]
  • Small Molecule FEP
    • Relative Solvation
    • Relative Binding
  • Solubility FEP:
    • Hydration
    • Dissolution
  • Protein FEP:
    • Selectivity
    • Thermostability
• Additional settings in Advanced Options Panel [2023-4]
  • Equilibration time
  • Simulation time is split into solvent/complex/vacuum
• Improved accessibility for submitting jobs to web services [2023-4]

Constant pH Simulations

• Trajectory Player: Improvements to the Lambda Dynamics [2023-4]

FEP+ Protocol Builder

• Ability to run FEP+ Protocol Builder on user defined submaps [2023-4]

Macrocycles

• Introduced the -parameter command line argument for macrocyclize.py to individually specify parameters [2023-4]
  • The -parameter argument expects a <key>=<value> argument, where <key> is one of several runtime parameters that can be inspected through the -write_param_file option.

Biologics Drug Discovery

• New method to predict risk of oxidation of methionine residues in proteins (command line) [2023-4]
• Enhanced antibody humanization by CDR grafting method supports grafting onto frameworks of non-human species (e.g. for murinization) (command line) [2023-4]
• Updated and expanded default human germline database for antibody humanization [2023-4]
• Simplified filtering and display of inter-chain and intra-chain disulfide bridges [2023-4]

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Support for RMM-DIIS diagonalization algorithms [2023-4]
• Option to compute effective charges (command line) [2023-4]
• Option to merge trajectories from multiple ab initio MD jobs (command line) [2023-4]
• Surface Energy: Option to add constraints to atom positions [2023-4]
• Surface Energy: Option to optimize lattice parameters [2023-4]

Optoelectronics

Product: Genetic Optimization (GA)

• Support for DeepAutoQSAR on Windows and Mac [2023-4]

KMC Charge Mobility

Product: MS Mobility

• Plot KMC Charge Mobility: Option to select plots to exclude from averaging [2023-4]

Materials Informatics

Product: MS Informatics

• ML Property: Support for downloadable custom property prediction models [2023-4]
• ML Property: Optoelectronic properties from custom downloadable models [2023-4]
• MD Descriptors: MD workflow to compute descriptors [2023-4]

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Support for Martini force fields refined for proteins [2023-4]
• Support for ‘tiny’ (T) type bead in Martini with 3.2 Å sigma [2023-4]
• Support for Martini cyclodextrin particles [2023-4]

Dielectric Properties

Product: MS Dielectric

• Summary tab in the viewer with organized output information [2023-4]
• Results estimation tool in the viewer for given density and polarizability [2023-4]

Reactivity

Product: MS Reactivity

• Auto Reaction Workflow: Module for comprehensive automated reaction analysis [2023-4]

MS Maestro Builders and Tools

• Elemental Enumeration: Option to select multiple elements from the periodic table [2023-4]
• Meta Workflows: Support for TDDFT and relativistic Hamiltonians in QM stages [2023-4]
• Meta Workflows: Support for multi-CPU/GPU setup in Individual stages [2023-4]
• Meta Workflows: Support for setting additional input files to be passed to a stage [2023-4]
• Meta Workflows: Standard output stored in the file system for custom stages [2023-4]
• Solvate System: Workspace action menu (WAM) [2023-4]
• Structured Liquid: Hydrophilic/Hydrophobic groups assigned as atom properties [2023-4]
• Structured Liquid: Visualization of arrow from hydrophilic to hydrophobic groups [2023-4]

Classical Mechanics

• Evaporation: User control over trajectory recording interval [2023-4]
• MD Multistage: Trajectory (CMS) stored for the stage prior to Average Cell stage [2023-4]
• Radial Distribution Function: Option to group by monomer [2023-4]

Quantum Mechanics

• Optoelectronics: Support for PCM solvent setup for redox potential predictions [2023-4]
• Reaction Energetics Enumeration: Support for multi-CPU subjobs [2023-4]
• Reaction Workflow: Option to run xTB optimization after conformational search [2023-4]
• Reaction Workflow: Turnover frequency from the energetic span model [2023-4]
• Transition Moment Order Parameter: Support for higher excited states [2023-4]
• Transition Moment Order Parameter: Additional options for excited state setups [2023-4]

Education Content

• New Tutorial: Molecular Dynamics Descriptors for Machine Learning [2023-4]
• New Tutorial: Design of Asymmetric Catalysts with Automated Reaction Workflow [2023-4]
• Update: Dielectric Properties [2023-4]
• Update: Liquid Electrolyte Properties: Part 1 [2023-4]

LiveDesign

What’s New in 2023-4

• Landing Page Improvements
  • Tag compounds as Favorites to pin them to the top of the Compounds page
  • Bookmarked LiveReports open in a new browser tab
  • View the total number of compounds, number of virtual compounds, and number of real compounds in a project
  • View recently added Real or Virtual compounds, and filter by date range
• Reorder SAR scaffolds to change the priority and control which scaffold compounds will match
• View column header icons for Formula and Freeform column to help identify the column type
• View an assay’s description in a tooltip when hovering over the column header in a LiveReport
• Rows that are added to a LiveReport after searching are automatically selected
• Model/Protocol Metadata UX Improvements
  • “Created By” field is added to the protocol/model details page
  • The number of depending models of each protocol is displayed in the protocol listing page
  • A direct link back to the protocol is provided in the model details page
  • Creation Date and Last Modified Date are added as new columns in the protocol/model listing page
  • Easier to access the “clear model results” option
• Faster LiveReport filters and R-group decompositions, with greater performance increases for larger LiveReports

What’s Been Fixed

• LiveReports that contain Layouts with one or more Matrix widgets can now be duplicated
• LiveReports that contain unpublished parameterized models with picklist parameters can now be duplicated
• Advanced Search
  • Advanced searches that used the Limit Multiple Endpoints treated inverted search conditions and normal search conditions the same, and now correctly distinguish between the two
  • Inverted advanced searches for experimental results with limiting conditions previously returned compounds that had no results, and now only return compounds with defined results
  • Advanced searches on experimental results, that include conditions using the Limit Multiple Endpoints feature, incorrectly returned results that did not match the Limit Multiple Endpoints search criteria, and now return results that match all criteria
• Uploaded experimental results from files for Generic Entities now appear in the Data & Columns tree
• Tasks listed in the Admin Panel would occasionally report their status as Submitted or Running, when the task was not actually Submitted nor Running, and now correctly report their status
• Powerpoint exports now use a grey background for the header column, and use the term Entity instead of Result for the compound image row
• Dragging the same compound to the sketcher multiple times in a row will correctly show the compound
• Coloring rules in plots now work correctly when the coloring rules are defined by a multi-select picklist Freeform column
• Selection navigation in the LiveReport footer now correctly scrolls within Tile View
• The Ligand Designer previously showed newly added fragments in a green color, and now show atoms using the default coloring scheme
• Loading a saved scene within the 3D visualizer now correctly styles ligands, based on the styling used when the scene was saved
• Custom binning within plots is now correctly saved in Forms view
• Users with the Viewer role no longer see a temporary red authentication error bar after logging in
• The notification “1 other person viewing this LiveReport” previously appeared long after a user closed the LiveReport, and now correctly shows when other users are viewing the LiveReport

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Apply ribbon and cartoon styling on selected entries  [2023-3]
• Improve visualization of interactions crossing Periodic Boundary Conditions [2023-3]
• Seamlessly copy and paste data from the Project Table into external applications including spreadsheets, enabling efficient data transfer and analysis [2023-3]
• Trajectory Player [2023-3]
  • View trajectories from lambda dynamics calculations such as those from the constant pH workflow
  • Navigate frames in trajectory visualization easily using keyboard arrow keys
• 3D Builder [2023-3]
  • Access Builder Behavior options from the 3D Builder palette
• Interactively mutate native nucleotides in the Workspace, including between DNA to RNA and RNA to DNA nucleotides [2023-3]
• Enhanced “Save Project As” functionality with Windows-only UX improvements [2023-3]
• Maestro to PyMOL connection [2023-3]
  • Streamline the integration of WaterMaps with PyMOL
  • Include Maestro Scene “Description” as a PyMOL Message for better scene management
• Maestro to LiveDesign connection [2023-3]
  • Seamlessly integrate between Maestro and LiveDesign with the new Mapping Manager. Easily rename property mappings and eliminate the issue of cluttered names when creating variations. Save and share mappings using the direct import and export feature.

Job Control

• Smart distribution jobs in Job Server now check license availability, eliminating risk of license exhaustion [2023-3]

Workflows & Pipelining [KNIME Extensions]

• Streamline the login process with the LiveDesign connection node using Single Sign-On (SSO) tokens [2023-3]

Target Validation & Structure Enablement

Protein Preparation

• Optionally use custom PFAM databases in pfam_driver.py [2023-3]
• Import structures into Coot with standard residue names from protein preparation’s PDB output. The Maestro output retains protonation-specific residue naming, i.e HIP/HID/HIE instead of HIS [2023-3]
• Significantly improved performance of Protein Preparation including the Interactive Optimizer for systems of 90,000 atoms or more [2023-3]

Multiple Sequence Viewer/Editor

• Benefit from speed and accuracy improvements in protein/nucleic acid structure alignment from replacing the previous SKA aligner with the CEAlign algorithm [2023-3]
• Download structural models directly from AlphaFold2 by providing a UniProt ID [2023-3]

IFD-MD

• Design out common ADMET liabilities using the new IFD-MD workflow (Beta). Predict complex structures of a ligand bound to CYP2D6, CYP3A4, PXR, or hERG [2023-3]

Hit Identification & Virtual Screening

Ligand Preparation

Empirical and QM-based pKa Prediction

• Benefit from improved accuracy with the addition of several hundred more data points in the Macro-pKa training set [2023-3]

Active Learning Applications

• Adjust equilibration simulation times and complex restraint options in Active Learning-FEP [2023-3]
• Connect to ongoing GraphDB runs when restarting Active Learning-FEP jobs [2023-3]
• Generate a final Maestro file that contains all ligands with FEP data and the corresponding endpoints [2023-3]

Shape Screening

• Screen up to tens of billions of compounds quickly and efficiently with the new Quick Shape ligand-based screening workflow [2023-3]

ABFEP

• Fit torsions on the fly via FFBuilder for FEP+ Web Services [2023-3]

Lead Optimization

FEP+

• Fit torsions on the fly via FFBuilder for FEP+ Web Services [2023-3]
• Support linker enumeration of compounds with symmetrical R-groups [2023-3]

Constant pH Simulations

• Full-featured release of constant pH simulations [2023-3]
• Improved analysis of constant pH simulations for protein pKa calculations [2023-3]
  • Automatically write constant pH trajectories specific to each pH
  • View trajectories from lambda dynamics calculations such as those from the constant pH workflow

Solubility FEP

• Fit torsions on the fly via FFBuilder for FEP+ Web Services [2023-3]

Quantum Mechanics

• Predict conformation-dependent IR and VCD/ECD spectra using an automated workflow within the new Jaguar Spectroscopy product [2023-3]
• Download importable Jaguar-formatted basis sets from Basis Set Exchange [2023-3]
• Access dynamic scans from the Relaxed Scan panel [2023-3]
• Access the ΔSCF method and a script to prepare ΔSCF input on the command line [2023-3]

Semi-Empirical Quantum Mechanics

• Parallelize batch and individual xTB calculations with OpenMP [2023-3]

Biologics Drug Discovery

• Protein Linker Design Panel: Automatically detect and populate terminal residue and corresponding distances for improved usability [2023-3]

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Quantum ESPRESSO: Upgrade to Quantum ESPRESSO 7.2 [2023-3]
• Quantum ESPRESSO: Support for Car-Parrinello MD (cp.x) (command line) [2023-3]
• Quantum ESPRESSO: Undo for atom reordering in NEB setup [2023-3]
• Quantum ESPRESSO: Support for data analysis for 3D-RISM (pprism.x) (command line) [2023-3]
• Quantum ESPRESSO: NEB Energy reported in Project Table [2023-3]
• Quantum ESPRESSO: Calculation and plot of Raman spectra [2023-3]
• Quantum ESPRESSO: Option to reduce scratch disk space requirement (command line) [2023-3]
• Quantum ESPRESSO: Faster job launch for large structures [2023-3]
• Surface Energy: Workflow module to compute surface energy [2023-3]

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Warning for molecular weight outside the model’s range [2023-3]
• Machine Learning Property: Viscosity prediction for molecular liquids [2023-3]

Dielectric Properties

Product: MS Dielectric

• Complex Permittivity: Improved assignment algorithm for CPU and GPU subjobs [2023-3]

MS Maestro Builder and Tools

• Square pyramidal geometry option from complex builders [2023-3]
• Extract Clusters: Jobs launched to queue [2023-3]
• Extract Clusters: Option to extract single molecules [2023-3]
• Meta Workflows: Option to set up implicit solvent in the QM stages [2023-3]
• Meta Workflows: Support for a workflow-splitter stage [2023-3]
• Meta Workflows: Support for workflow-split by polymer builder stage [2023-3]
• Meta Workflows: Support for workflow-split by disordered system builder stage [2023-3]
• Meta Workflows: Support for workflow-combine stage following a workflow-split [2023-3]
• Meta Workflows: Incorporation of all structures from each stage [2023-3]
• Meta Workflows: Built-in stage for Extract Clusters [2023-3]
• Meta Workflows: Built-in stage for Conformational Search [2023-3]
• Meta Workflows: Built-in stage for Evaporation [2023-3]
• Meta Workflows: MD trajectories saved by default for single stage workflows [2023-3]
• Meta Workflows: Preceding stage set as parent by default for a new stage [2023-3]
• Query Bonds: Options to selectively show bonds through periodic boundaries [2023-3]
• Solvate System: Advanced builder for a solvated systems with 100K+ atoms [2023-3]

Classical Mechanics

• Barrier Potential for MD: Tool to set up repulsive barriers for MD simulations [2023-3]
• Electrolyte Analysis: Support for polyatomic ions [2023-3]
• Evaporation: Default length for each MD stage set as 20 ps [2023-3]
• Molecular Deposition: Improved simulation speed [2023-3]
• Molecular Deposition: Support for repulsive potential barrier [2023-3]
• Polymer Crosslink: Image export from the viewer with 300 dpi [2023-3]

Quantum Mechanics

• Reaction Workflow: Support for post-MacroModel XTB optimization [2023-3]
• Reaction Workflow: Check to avoid non-minimum stationary states [2023-3]
• Transition Moment Order Parameter: Workflow module to compute order parameter based on transition dipole moment [2023-3]

Education Content

• New Tutorial: Applying Barrier Potentials for Molecular Dynamics Simulations [2023-3]
• New Tutorial: Building Solvated Systems [2023-3]
• New Tutorial: Dynamic Relaxed Coordinate Scans [2023-3]
• New Tutorial: Calculating Transition Dipole Moments (TDM), TDM Distributions, and Order Parameter [2023-3]
• Update: Molecular Deposition [2023-3]
• Update: Modeling Surfaces [2023-3]
• Update: Polymer Electrolyte Analysis [2023-3]

LiveDesign

What’s New in 2023-3

• Assay Viewer Tool enhancements
  • Filter data by experiment date
  • Highlight cells in the LiveReport that match data in the Assay Viewer
  • Use keyboard arrow keys to navigate rows
  • Select multiple rows at once
• Coloring Rules: Quickly transfer coloring rules from any column to any other column by copying and pasting coloring rules through the column menu
• Ligand Designer: Convert a Parameterized Glide Model to an implicit Ligand Designer configuration, for example with FEP+ poses uploaded from Maestro
• Maestro Export Enhancements
  • Map Maestro to LD properties to streamline frequent exports
  • Log in with single sign-on
  • Log in once and reuse the session across multiple export actions
• UX Improvements
  • 3D Visualizer
    • Pi-pi interactions are shown by default within the 3D visualizer
  • Experimental Data Handling
    • Add hyperlinks to Assay Tooltips to quickly navigate to any website
  • General LiveReport Improvements
    • Quickly navigate to selected compounds by using new navigation buttons in the LiveReport footer
    • Find LiveReports more quickly through the LiveReport Picker, which opens the most recently accessed folder
    • Filters now shows a yellow notification bar after making any change
    • Notification bars now include a ‘x’ button to remove the notification
    • Close all open LiveReports by clicking a new “Close All” option in the LiveReport menu
  • Landing Pages
    • Hyperlinks in the Landing Page automatically open in a new tab
    • The Landing Page’s “Recently Commented Compounds” list now include a hyperlink to quickly navigate to the compound’s detail page
  • Plots
    • Move the compound image within plot tooltips
    • Box plots now show a solid blue color for each box
    • View accurately scaled plot overlays when the axis is set to logarithmic scale
  • Search
    • Search the active LiveReport for multiple IDs at once and delete multiple IDs
    • Filter GPUSimilarity search results with computed property thresholds
    • A clear button is available to reset the list of IDs in Search by ID
    • Searches within the Data & Columns tree now span across folders and column names to find matches, rather than looking for matches only within a continuous folder name or column name
  • Quickly select Experiment Protocols within the Generic Entity import UI with a new typeahead suggestion

What’s been fixed

• Structure searches now correctly use the sketched structure after navigating between LiveReports and Landing Pages
• Parameterized models that use MPOs as input now calculate when the MPO does not have a score
• The Assay Viewer Tool can not longer delete Freeform column data
• Compounds that get added to LiveReports with R-group decompositions now have their decomposed R-groups correctly colored without hard-refreshing the LiveReport
• The Admin Panel Tasks list and Task Details Page now show the correct LiveReport ID that launched the task, after compounds are copied from one report to another and the model is recalculated
• The Apply Template dialog now denotes which templates belong to the Global project, and lists the templates in alphabetical order
• The Structure Processing UI within the Admin Panel shows structures more quickly
• The Structure Processing interface within the Admin Panel now shows a loading indicator when uploading a processing file
• Forms widgets now show a hammer and wrench icon to quickly access the Ligand Designer
• Plots within Forms now show a tooltip when expanding the legend
• The column header’s dropdown button is now visible after selecting multiple columns that extend beyond the screen width
• Searching the LiveReport via the magnifying glass will now correctly scroll to results when the LiveReport has frozen rows
• The Add and Change Model pages within the Admin Panel now list protocols alphabetically within the Parent Protocol dropdown
• Navigating to a URL within the User Manual will correctly redirect to the User Manual page after logging in
• Forms with long titles no longer alter the Form Toolbar’s alignment
• Plot tooltips now permit reordering the list of properties
• The LiveReport Picker UI is now consistent between Firefox and Chrome, and no longer highlights text after selecting multiple LiveReports via Shift+Click or Ctrl+Click (Cmd+Click on Mac)
• The Tile view scroll bar no longer changes size while scrolling
• Clicking on the Project Name in the upper left hand portion of the user interface will now open the Project Selection dialog
• Freeform column descriptions can now be deleted when configuring a Freeform column
• The Column Management panel now indicates which groups contain both visible and hidden columns
• Tile view now shows and hides stereo annotations when using the “Show Stereo Annotations” toggle
• Searching the LiveReport via the magnifying glass will now show results after filters conditions are removed
• Password resets no long fail, which prevented password resets and adding new users
• LiveReports that contain Layouts with one or more Matrix widgets can now be duplicated
• Ligand Designer sessions no longer show a message that zero docking jobs are queued when the docking queue is empty
• Uploaded experimental results from files for Generic Entities now appear in the Data & Columns tree
• Templates from the Global project can no longer be overwritten from another project
• Columns from unpublished Maestro uploads and file uploads of small molecules no longer appear in the Data & Columns tree
• Reactions will now show the reaction image, and successfully compute, after a reaction is selected via double-clicking

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Added support for interactive nonstandard protein residue mutation via the Workspace context menu [2023-2]
• Save up to 5K resolution GIFs (Workspace -> Animate) [2023-2]
• Reduce unexpected visual clutter with new preference to limit the number of atom labels [2023-2]
• Maestro to PyMOL connection [2023-2]
  • Create a simple PyMOL movie from Maestro scenes
• Maestro to LiveDesign connection [2023-2]
  • Connect to LiveDesign servers with new access point and connection status indicator
  • Retain and reuse single sign on (SSO) tokens to streamline the login process
  • Benefit from a streamlined process of pushing Maestro data into LiveDesign via the Export panel
• Export Structures – New option to export MD-ready structure / trajectory to CMS file [2023-2]
• New “Show Atom Properties (beta)” panel [2023-2]
  • List multiple atom properties for selected atoms
  • Display SMARTS/SMILES patterns for contiguous selected atoms, including the SMARTS index of the hovered-over atom

Workflows & Pipelining [KNIME Extensions]

• Includes the latest version of KNIME [2023-2]
• Improved usability of the Extract Properties node configuration panel [2023-2]
• Updated LiveDesign nodes and protocols: [2023-2]
  • Adaptable input column checking of the LiveDesign input node
  • KNIME protocol section to install extra KNIME extensions is more robust

Target Validation & Structure Enablement

Protein Preparation

• Bond orders and charges can now either be re-assigned or only added to ligands and residues with missing bond orders [2023-2]

Protein X-Ray Refinement

• Improved robustness when running Phenix/OPLS [2023-2]
• New plots to inspect the best refinement statistics from Phenix/OPLS weight scans [2023-2]
• Phenix/OPLS weight scan automatically choses a near-optimal combination of refinement parameters [2023-2]

AlphaFold Download / Process

• Downloaded AlphaFold structures are returned with an automatically created heatmap of the PAE matrix [2023-2]
• Processed AlphaFold structures can now be optionally capped and the pLDDT threshold changed [2023-2]

Multiple Sequence Viewer/Editor

• New ability for the detection and annotation of Vernier zone residues in antibodies [2023-2]

IFD-MD

• Added visual indicator when the target ligand is missing torsional parameters [2023-2]

Desmond Molecular Dynamics

Improved plotting for Trajectory Plots [2023-2]

Hit Identification & Virtual Screening

Ligand Preparation and Conformation Generation

• Full support for Epik 7 pKa predictions within the LigPrep interface and command line invocation [2023-2]

Empirical and QM-based pKa Prediction

• Conjugate acid/base labels are now included in the Epik 7 log file [2023-2]

Hit Analysis

• Release of the new Hit Analysis interface to streamline interactive analysis and selection of hits from virtual screening campaigns based on molecular properties, ligand feature locations, and shape alignments [2023-2]

Active Learning Applications

• Added ability to train on preexisting FEP data for relative and absolute AL-FEP [2023-2]
• Added histogram of compounds prioritized by machine learning for relative and absolute AL-FEP [2023-2]
• Modified default machine learning settings to improve out-of-the-box performance of relative and absolute AL-FEP [2023-2]

ABFEP

• New capability for fast filtering of inactive ligands to dramatically improve ABFEP throughput [2023-2]

Lead Optimization

Macrocycles

• Improved atom mapping in FEP+ maps for macrocycles [2023-2]

FEP+

• New functionallity to auto-populate state populations in the FEP+ interface [2023-2]
• Improved reporting of results in a single column (val ± err) in the overview tab of the FEP+ interface [2023-2]
• Option to automatically merge force field parameters generated during an FEP+ job with those defined in your Maestro preferences [2023-2]
• Option to select alternative water models for Relative Binding FEP+ via Advanced settings [2023-2]
• Fast filtering of inactive ligands to dramatically improve ABFEP throughput [2023-2]
• Improved atom mapping in FEP+ maps for macrocycles [2023-2]

Protein FEP

• Ability to simultaneously predict protein thermostability with every protein/ligand selectivity simulation [2023-2]
• Option to interactively edit perturbation topologies for protein residue mutations in FEP+ interface [2023-2]

Constant pH Simulations (Beta)

• Greatly improved accuracy in protein pKa predictions through improved sampling of the physical end states of titratable residue side chains in FEP+ [2023-2]

Quantum Mechanics

• New ability to plot excited state energies in rigid and relaxed coordinate scans [2023-2]
• Support for alignment based on uniform scaling in the VCD/IR spectrum_align utility [2023-2]

Semi-Empirical Quantum Mechanics

• Capability to use GFN2-xTB from within Jaguar and in Jaguar-based workflows [2023-2]

Biologics Drug Discovery

• Improved protein descriptor calculation throughput with ability to run in parallel over multiple CPUs [2023-2]
• Up to 5x speedup in protein surface calculations [2023-2]
• Modeling of single-chain Fvs is now incorporated into the antibody structure-prediction interface [2023-2]
• Modeling of F(ab)2 formats is now integrated into the antibody structure-prediction interface [2023-2]
• MSV is now accessible directly from the protein-protein docking interface [2023-2]
• Selected entries in antibody database management interface can now be exported to MSV and Maestro [2023-2]

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Quantum ESPRESSO: Reduced disk usage with hybrid functionals [2023-2]
• Quantum ESPRESSO: Option to import only the final structure in QE import GUI [2023-2]
• Quantum ESPRESSO: Automatic q-point mesh setup with hybrid functional [2023-2]

Transport Calculations via MD simulations

Product: MS Transport

• Diffusion Coefficient Viewer: Visualization of atoms selected for diffusion tracing [2023-2]
• Viscosity: Expanded range of shear stress available for analysis [2023-2]

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Report of entries with failed predictions if any [2023-2]
• Machine Learning Property: Density prediction for molecular liquids [2023-2]
• Machine Learning Property: Models to measure uncertainties from the predicted properties [2023-2]

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• CG FF Builder: Better defaults for convergence [2023-2]
• CG FF Builder: Option to set initial values [2023-2]
• CG FF Builder: Option to save the force field file in viewer [2023-2]

Dielectric Properties

Product: MS Dielectric

• Complex Permittivity: Option to adjust the length of dipole moment sample extracted from the source trajectory (command line) [2023-2]

MS Maestro Builders and Tools

• Crystal: Edit option for lattice parameters when importing PDB without them [2023-2]
• Manipulate Cell: Option to take multiple entries as input for selected operations [2023-2]
• Meta Workflows: Support for molecular QM simulation stages [2023-2]
• Meta Workflows: Option to compute ESP charges for subsequent stages [2023-2]
• Semicrystalline Polymer: Improved robustness and speed for building semicrystal interface [2023-2]

Classical Mechanics

• Crystal Morphology: Improved pop-up guideline for setting a proper input cell size [2023-2]
• Improved UI to select atoms for substrate restraints in MD-based workflow panels [2023-2]
• Droplet: Option to take existing MD simulation trajectory as input [2023-2]
• Droplet: Support for built-in and custom solvents for contact angle prediction [2023-2]
• Electroporation: Workflow module to simulate and assess membrane electroporation [2023-2]
• Evaporation: Redesigned UI for the workflow setup panel [2023-2]
• Evaporation: Support for evaporating multiple solvents [2023-2]
• Evaporation: Added flexibility to evaporation zone definition [2023-2]
• Evaporation Results: Load structures from one or more iterations into the Project Table [2023-2]
• MD Multistage: Support for negative external electric field [2023-2]
• MD Multistage: Option to remove center of mass velocity [2023-2]
• Stress Strain: Support for sinusoidal loading (command line) [2023-2]

Quantum Mechanics

• Adsorption Enumeration: Option to set bridging and hollow sites for adsorption [2023-2]
• Complex Enumeration: Report of the ligand exchange stability in Project Table [2023-2]
• Prediction of singlet excitation energy transfer rates (SEET) (command line) [2023-2]

Education Content

• New Tutorial: Calculating Voltage Curves on Spinel Intercalation Compounds [2023-2]
• New Tutorial: Machine Learning for Ionic Conductivity [2023-2]
• New Tutorial: Electroporation [2023-2]
• Update: Evaporation [2023-2]
• Update: Droplet Contact Analysis [2023-2]
• Update: Viscosity [2023-2]
• Update: Machine Learning Property Prediction [2023-2]

LiveDesign

What’s New in 2023-2

Kubernetes versions of LiveDesign include:

• Composite Rows
  • Create relationships between entities to better view the composition of complex mixtures, linking them as subcomponents and showing them as indented rows.
  • Get a better understanding of drug formulations by viewing the components that make up the mixture
  • Better define the composition of stereoisomeric mixtures
  • Analyze the differences between different battery electrolyte formulations

All versions of LiveDesign include:

• Forms
  • Show data in a custom, dense arrangement with the Matrix widget
  • Search for compound IDs directly in the Compound Image widget
  • Set up forms more quickly, and identify columns to add to widgets more quickly, with an updated column shuttle
  • Collapse or expand all swimlanes in Kanban widgets using a menu option
  • Form widget titles automatically expand to show longer widget titles when a single widget is within a window
• View any custom Experimental Metadata in the assay tooltips
  • Any metadata can be added to LiveDesign from corporate assay capture systems through the Data Integrator
• Generic Entity – store, model, and analyze any kind of modality in LiveDesign
  • Purge and Overwrite experimental data
  • Append new data to a Lot
• 3D Visualizer
  • View halogen bond and salt bridge interactions
  • Show Chain ID in the residue label
• Significant improvements to streamlining integration of Maestro sessions and LiveDesign servers
  • Benefit from visual notice in Maestro of connected LiveDesign servers, user account recall, and automatic connection to LiveDesign with valid single sign-on
• UI and UX Improvements
  • Independently size column groups and column headers in the LiveReport spreadsheet view
  • View column metadata in tooltip by hovering over a column title in the spreadsheet
  • View the true data point color in Plots after selecting data points
  • Expand and collapse the plot legend to avoid obscuring data points
  • Remove compound images from Plot tooltips
  • Resize columns in the Assay Data Viewer tool
  • Switch between row-per modes more easily
  • Use angle bracket and ampersand characters in formulas for manipulating strings, such as the split() formula
  • Importing compounds through a file and matching by IDs will now skip rows that do not have a match, and report which IDs failed to import

What’s Been Fixed

• Cell coloring rules no longer extend beyond the edge of a tile
• Data & Columns tree tooltips show the correct “View” button or “Edit” button for columns, based on each users’ assigned permissions
• Date and Datetime display formats set within the Admin Panel now apply to all users with a role set to ‘User’
• Editing a picklist Freeform column value in a Kanban widget will immediately update the tile’s location within the Kanban widget
• Filter conditions for formula columns that include substructure images will correctly show the substructure images
• Filter conditions on columns that have file attachments no longer show file IDs in the suggestion dropdown
• Forms correctly show a pointer cursor instead of a grab cursor when viewing the form
• Forms now support drilldown from Kanban widgets to Spreadsheet and Table widgets
• Forms now support multiple instances of the same custom tool
• Histogram and Pie plots permit creating a defined number of equally distributed bins
• Histogram plots within Forms now permit defining custom bins
• LiveDesign will start even if the preprocessor config includes unsupported fields
• MPO desirability cell borders no longer show a color when the color is defined by a proxy value
• MPO tooltips now appear in Form widgets that have a drilldown selection
• Picklist Freeform columns now permit bulk copying dates from assay columns
• Plots that use the Highlighted Substructure column will now show compound images when defining custom bins in Histogram and Pie charts
• Plots with a regression line will correctly scale when the plot axes are converted to log scale
• Plots with log axes no longer show negative values
• Reagents with numeric IDs will correctly carry through their data when used within Reaction Enumeration
• Scatter plots with three axes and many data points no longer show blank exports
• Selecting a range of tiles in a Kanban widget, while holding down the shift key on the keyboard, will now only select the visible tiles within a vertical
• The maximum number of data points allowed within a plot, set within the Admin Panel, now applies to all users with a role set to ‘User’
• Toggling to different plot tabs in Forms will now show the correct data point tooltips
• Typed text within filter conditions, that has not been saved, is now removed after selecting an option from the dropdown list