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 Upcoming in 2025-2

• Enhanced support for antibody-drug conjugates: Import ADCs from a source database and view the entire subcomponent hierarchy in the spreadsheet
• Improved collaboration with freeform column comments: View a comment thread in the main spreadsheet and enable a structured, context-specific conversation with user attribution and timestamps
• Ability to standardize workflows with form templates: Create a standardized data view or analysis, and add the Form to other LiveReports
• New and updated protocols: The FEP+ Pose Builder Protocol has been updated and a new FEP+ Amenability Protocol returns additional pose quality metrics.

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

• 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

• 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 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

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Simultaneously mutate multiple selected nucleotides [2023-1]
• Quickly select “Nucleic Acids” substructures in the Custom Sets editor dialogs [2023-1]
• New Custom Presets functionality [2023-1]
  • Option to export subset of only selected presets
  • Expanded control with “Color by Element (Chain Name Carbons)” option
• Improved “Maestro to PyMOL” capabilities [2023-1]
  • Improved discovery of “Send to PyMOL” option by moving it to the File menu
  • Option to include trajectory data in “Send to PyMOL”
• Preference to “Keep center of rotation fixed while translating” now enabled by default [2023-1]
• Project Table / Entry List improvements [2023-1]
  • Automatically scroll to the original row of a Shortcut Row entry with a double-click
  • Select rows where any of the included entries have atoms selected in the Workspace
• Show/hide pharmacophore feature labels with the Annotations toggle [2023-1]
• BioLuminate [2023-1]
  • Quickly select antibody-related segments such as CDRs, Fab, Fv and others with predefined selection sets
• View, analyze and share molecular vibrations information with new Vibrations panel [2023-1]
  • Easy-to-use playback controls and tight interaction with the Workspace
  • Save frames from vibration frequency animation as 3D structures
  • Communicate with colleagues through exported movies of selected modes

Workflows & Pipelining [KNIME Extensions]

• Support for KNIME (v4.7) added [2023-1]
• Enhanced robustness of the Extract Properties node where new properties can now be included or excluded [2023-1]
• The LigPrep node now reads setting files exported from Maestro [2023-1]
• The new Protein Preparation Workflow node configuration panel is identical to Maestro’s [2023-1]
• Improvements to LiveDesign Import and Export nodes [2023-1]
  • Move beyond ligands and proteins to import any 2D/3D structure into LiveDesign as generic entities
  • Import entire LiveReports into KNIME for analysis

Target Validation & Structure Enablement

Protein Preparation

• Small peptides (< 200 atoms) can now also optionally be capped [2023-1]

Multiple Sequence Viewer/Editor

• Use the Protein Family Alignment feature to align and annotate new sequences to a user supplied reference set for all protein families (beta) [2023-1]
• Generate complement and reverse complement sequences for Nucleic Acid chains [2023-1]

Desmond Molecular Dynamics

• Improvement in performance up to 1.17X (17%) in ns/day throughput realized from collaboration with NVIDIA. The largest speed improvements from running on modern GPUs with small to moderate sized systems [2023-1]

QM/MM (Qsite)

• More robust and reliable minimizations from switching default minimizer from truncated newton to conjugate gradient [2023-1]
• Added support for dispersion-corrected functionals including DFT-B3LYP-D3, DFT-M06-2X-D3, DFT-B3LYP-D3(BJ), DFT-M06-2X-D3(BJ), DFT-wB97X-D, and DFT-B97-D3 [2023-1]

AutoQSAR

AutoQSAR & DeepAutoQSAR

• Normalize numeric additional features to eliminate instability in network training in case of very large or small values [2023-1]

Hit Identification & Virtual Screening

Shape Screening

• Easily restart Shape GPU calculations from the command line [2023-1]

Lead Optimization

FEP+

• Significant performance improvements of up to 1.4X in FEP+ perturbations/day realized from collaboration with NVIDIA. The greatest speed boosts are observed on larger core count GPUs with small to moderate sized systems [2023-1]
• Improved interface usability when handling groups, including how values are applied to maps [2023-1]
• Automatically calculate protomer/tautomer/conformer populations using Epik7 with fep_groups.py script [2023-1]

Quantum Mechanics

• Easily hide and redisplay spectra in the Spectrum Plot interface [2023-1]
• Added support for rSCAN, r2SCAN, and r2SCAN-D3(BJ) DFT functionals [2023-1]
• Added support for thirty-four D4 dispersion corrected functionals [2023-1]

Semi-Empirical Quantum Mechanics

• Switch from MOPAC7.1 to MOPAC2016 calculation engine for Semiempirical interface [2023-1]

Medicinal Chemistry Design

Ligand Designer

• Design for ligand selectivity through visualization of binding site volumes accessible to only one of two receptors and identifying ligands that dock well into only one of two receptors (beta) [2023-1]

Biologics Drug Discovery

• Perform simultaneous back mutations of multiple residues in Antibody Humanization using the CDR grafting workflow [2023-1]
• Quickly select antibody-related segments such as CDRs, Fab, Fv and others with predefined selection sets [2023-1]
• Connect data to structure in Residue Scanning where selecting residues in the Workspace now also selects the residues in the Residue Scanning table [2023-1]
• ‘Crosslink Protein’ interface has been renamed to ‘Protein Linker Design’ to more accurately reflect its purpose. and now includes access to a choice of two loop library databases, one for constructing intradomain linkers and the other for inter-domain linkers [2023-1]

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Quantum ESPRESSO: Improved scalability and versatility of NEB workflow [2023-1]
• Quantum ESPRESSO: Support for RISM-3D (command line) [2023-1]
• Quantum ESPRESSO: Dimer method for finding transition states (command line) [2023-1]
• Quantum ESPRESSO: Option to apply Niggli reduction (command line) [2023-1]

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Boiling point prediction over a range of pressure [2023-1]
• Machine Learning Property: Interactive prediction for up to 10 selected entries [2023-1]

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Improved loading speed for a CG system in trajectory viewer [2023-1]
• CG FF Builder: Warning from *.log for discrepancy in reduced density [2023-1]
• CG FF Builder: Support for force constants with zero angles [2023-1]
• CG FF Assignment: Improved UI for setting reduced density and cutoff distance [2023-1]
• CG FF Assignment: Support for populating reduced density from the FF file [2023-1]
• CG FF Assignment: Warning for CG particles with large differences in radii [2023-1]

Molecular Dynamics

Product: Desmond

• Improvement in performance up to 1.17X (17%) in ns/day throughput realized from collaboration with NVIDIA. The largest speed improvements from running on modern GPUs with small to moderate sized systems [2023-1]

MS Maestro User Interface

• Periodic boundary condition accounted for evaluating “within/beyond” ASL [2023-1]

MS Maestro Builders and Tools

• Manipulate Cell: Option to shift origin [2023-1]
• Meta Workflows: Module for building and running multiple connected workflows [2023-1]
• Polymer: Support for monomers marked by Mark Head and Tail (command line) [2023-1]
• Query Bonds: Zoom to a bond selected in a row from the panel [2023-1]
• Structured Liquid: Expanded list of built-in lipids [2023-1]

Classical Mechanics

• Droplet: Module to predict contact angle of water droplet on a given substrate [2023-1]
• Evaporation: Workflow module to simulate evaporation with molecular dynamics [2023-1]
• Molecular Deposition: Allow to request only one MD per iteration [2023-1]
• Prepare for MD: Option to scale DPD systems based upon the force field [2023-1]
• Prepare for MD: Additional post-processing for Martini 2.x (command line) [2023-1]

Quantum Mechanics

• Complex Enumeration: Support for non-metal center in complex stability analysis [2023-1]
• Macro pKa: Option to assign active atoms in the course of generating tautomers [2023-1]

Education Content

• New Tutorial: Meta Workflow [2023-1]
• New Tutorial: Water Droplet Contact Analysis [2023-1]
• New Tutorial: Liquid Electrolyte Properties: Part 1 [2023-1]
• New Tutorial: Liquid Electrolyte Properties: Part 2 [2023-1]

LiveDesign

What’s New in 2023-1

• Project Overview Landing Page: View summarized landing page information
• Vertical only Kanban: Create a Kanban view using a single picklist Freeform column
• Forms
  • Use keyboard controls with the Compound Image widget to navigate from one compound to another
  • Define independent column widths for each widget
• Generic Entity: Store Lot and Experimental data on any chemical, biological, or material matter with any representation
• New enhancements to existing features, such as:
  • View the regression equation on scatter plots
  • Admins can log out users by removing their assigned Roles, or by specifying a specific username
  • Removing a single enhanced stereochemical AND group with the structure processor now defines the stereocenter as ‘undefined’, and previously would define is as an absolute stereocenter
  • Use advanced atom query features in substructure filtering
• Performance Improvements
  • SAR analysis tasks are performed asynchronously and take less time to complete
  • The 3D visualizer is more responsive when large proteins are viewed

What’s Been Fixed

• Models that returned a single value now show the full result unaligned with other columns
• The 3D visualizer uses the high performance GPU on client computers to avoid crashes
• Pasting multiple values into ID search will attempt to automatically identify the delimiter, or present an option to select the delimiter, by which to separate values
• Limited Assay Columns are now included in Matched Molecular Pairs analyses
• Pasting multiple values into Filters will attempt to automatically identify the delimiter, or present an option to select the delimiter, by which to separate values
• File import receipts show a scroll bar for errors parsing SD files
• Pinned plot tooltips in forms update the connecting line when the view is resized
• The file import receipt now shows IDs from SD file title lines
• Overlay lines in plots will now extend to the full plot dimensions
• Automatically generated coloring rules for R-groups, Scaffolds, and String columns that were created through the plot interface will now appear in plots
• Pinned tooltips now point to the correct data points in box plots
• The radar chart legend now shows which compound IDs are out of range by hovering over the “Out of Range” entry in the plot legend
• Multi-parameter optimization column dialogs appeared to allow unauthorized users to edit the definition, however any edits submitted were not saved. The dialog now shows all fields as disabled to unauthorized users.
• LiveReports set to Read-Only no longer allow users to configure Tile View
• Line charts no longer show R-groups as SMILES strings in the plot legend, and instead show images
• Forms with many narrow widgets not longer show errors when editing the Form
• Dragging to select multiple histogram bars will select all of the compounds within the bin

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Create and share custom visualization Presets  [2022-4]
• Added support to mutate DNA/RNA to standard nucleobases  [2022-4]
• New Workflow Action Menu to guide to next steps for Plot Rigid/Relaxed scans [2022-4]
• First full release of the new 2D sketcher [2022-4]
• Get Going with Maestro Video Series added to Documentation [2022-4]

Workflows & Pipelining [KNIME Extensions]

• Includes the latest version of KNIME (v4.6.1) [2022-4]
• The number of matches can now be controlled in the Phase screening node [2022-4]

In LiveDesign:

• When deploying a model the suitable KNIME protocol is chosen automatically and the latest version of the protocol uploaded [2022-4]
• Distribution of calculations is controlled from the model admin page [2022-4]
• Model changes from the LiveDesign Admin page can be preserved when overwriting an existing model [2022-4]
• A new administration node to move, archive and unarchive models [2022-4]

Target Validation & Structure Enablement

Protein Preparation

• Significant speedup when opening the Protein Preparation Workflow interface on Windows [2022-4]
• Reduced verbosity of Protein Preparation Workflow log file by limiting irrelevant CCD bond assignment error notices [2022-4]
• Protein Reliability Report will generate TEST reflections on-the-fly, if not available in provided .cv file, and report RSCC values [2022-4]
• Updated PROPKA to (latest) version 3.4 [2022-4]

Protein X-Ray Refinement

• Introduction of GlideXtal command line tool for automatic ligand fitting in crystallographic electron density maps [2022-4]
• PrimeX minimization is able to use structure factors in CIF format [2022-4]
• In Phenix/OPLS can now remove all entities clashing with crystal mates [2022-4]
• Phenix/OPLS is more robust to missing atoms in standard residues [2022-4]

Cryo-EM Model Refinement

• Beta GlideEM interface for ligand placement into cryo-electron density maps [2022-4]
• GlideEM now accepts gzipped (CCP4, MRC, MAP) files as input [2022-4]

Multiple Sequence Viewer/Editor

• Beta release of Protein Family Alignment and Annotation [2022-4]
  • A new category named ‘Family Feature Calculation’ located in the ‘Other Tasks’
  • Menu exposes protein family alignment and annotation
  • Supports kinase and GPCR Alignments
  • Supports annotation of GPCR regions
• Dendrogram hover tooltip to display distance information [2022-4]

IFD-MD

• Membrane-bound IFD-MD tutorial [2022-4]
• Covalent ligand IFD-MD tutorial [2022-4]

FEP+

• Show user-friendly message when undefined stereochemical centers are introduced [2022-4]
• Improved usability of FEP+ group panel to manage protonation and tautomeric states ensemble – for more accurate ΔΔG predictions [2022-4]

Constant pH Simulations (Beta)

• Improved usability of constant pH simulations for protein pKa calculations with friendly outputs [2022-4]

AutoQSAR

• Added MACCs keys for ligand featurization in DeepAutoQSAR [2022-4]
• Include ElasticNetCV model (strongly l1/l2 regularized linear regression) in DeepAutoQSAR hyper-parameter optimization [2022-4]
• New DeepAutoQSAR command line utility for greater ease-of-use [2022-4]

Desmond Molecular Dynamics

• In Trajectory Plots view Ramachandran plot of Protein Residues [2022-4]

Empirical and QM-based pKa Prediction

• Initial release of Epik 7, a new machine learning based application for fast pKa value and protonation state prediction [2022-4]
  • Epik 7 can also produce a plot giving the populations of states as a function of pH

Solubility FEP (Beta)

• Option to show solubility results in logS unit [2022-4]

Quantum Mechanics

• Calculate ESP charges for excited states under the TDDFT/TDA approximation [2022-4]
• Complete calculations faster with parallel Jaguar calculations on Windows [2022-4]
• New Workflow Action Menu to guide to next steps for Plot Rigid/Relaxed scans [2022-4]
• Over 80 examples of Jaguar input files in documentation [2022-4]

Semi-Empirical Quantum Mechanics

• GFN2-xTB method now available in the Semiempirical Module panel [2022-4]

Biologics Drug Discovery

• To improve protein linker design, the loop database was updated to a new version specifically intended for interdomain linker design [2022-4]
• To expand chemical liability detection, Asp isomerization pattern and free cysteine detection were added to the Reactive Residues interface [2022-4]
• New command-line script for running Protein Interaction Analysis with the ability to export results to csv format [2022-4]
• First full release of Protein Descriptors interface which now supports .mae and .maegz files containing multiple structures [2022-4]
• Copy-paste sequences into Antibody Structure Prediction interface under new “Enter new sequence” option [2022-4]
• Reuse the same input csv file format for batch homology modeling in Antibody Structure Prediction when running from the command line or Maestro [2022-4]
• Added support for ‘keep glycan’ option in Antibody Structure Prediction during batch modeling [2022-4]
• Cysteine scanning panel for disulfide design now supports remote job submission which is useful for running large jobs e.g. using when MD trajectory as input [2022-4]
• Added “Antibody-Antigen” to Interactions scope dropdown [2022-4]
• Get Going with BioLuminate Video Series added to Documentation [2022-4]

Materials Science

GUI for Quantum ESPRESSO

• Quantum ESPRESSO GUI: Option to hide selected atoms [2022-4]
• Quantum ESPRESSO GUI: Upgraded NEB UI for improved UX [2022-4]
• Quantum ESPRESSO: Endpoints saved for NEB mae files at each iteration [2022-4]
• Quantum ESPRESSO: Reduced file size for custom saved NEB setups [2022-4]
• Quantum ESPRESSO: Use of automatic parallelization with GUI support [2022-4]
• Quantum ESPRESSO: -save_failures option for driver (command line) [2022-4]
• Quantum ESPRESSO: -last_only option for qe2mae tool to save the final structure only  (command line) [2022-4]
• Quantum ESPRESSO: HUBBARD options enabled in input *.cfg (command line) [2022-4]
• Quantum ESPRESSO: Automatic restart for long AIMD simulations [2022-4]
• Quantum ESPRESSO: Support for cell volume relaxation [2022-4]

Molecular Dynamics

• Viscosity: ”,” used as the delimiter in CSV output for Einstein-Helfand analysis [2022-4]

Materials Informatics

• Machine Learning Property: Pre-built, validated machine learning models for a selective list of materials properties [2022-4]
• Molecular Descriptors: Report of semiempirical HOMO-LUMO gap [2022-4]
• Molecular Descriptors: Support for plotting molecular orbitals [2022-4]

Coarse-Grained (CG) Molecular Dynamics

• Support for Ewald sums with Martini force field [2022-4]
• CG FF Builder: Option to export the viewer data to CSV [2022-4]
• CG FF Builder: Support for the use of existing trajectory [2022-4]
• Map Atoms to Particles: Option to map selected atoms from the input structure [2022-4]

Penetrant Loading Simulation

• Penetrant Loading: Robust handling of GCMC water models [2022-4]
• Penetrant Loading: Visualization of periodic unit cell for the output structures [2022-4]

MS Maestro User Interface

• Resized Trajectory Analysis task frame in Maestro for better user experience [2022-4]

MS Maestro Builders and Tools

• Complex Builder: Expansion of ligand library [2022-4]
• Disordered System: Option to generate cells with different numbers of molecules [2022-4]
• Elemental Enumeration: Jobs launched to queue instead of running interactively [2022-4]
• Manipulate Cell: Option to translate within -0.5 and 0.5 of the fractional coordinate [2022-4]
• Manipulate Cell: Support for change of lattice dimensions without FF retyping [2022-4]
• Query Bonds: Option to export output to CSV [2022-4]
• Semicrystalline Polymer: Option to use existing crystal (command line) [2022-4]
• Semicrystalline Polymer: Reporting percentage of crystallinity [2022-4]
• Semicrystalline Polymer: Speed-up for building with polymer models [2022-4]

Classical Mechanics

• MD Multistage: Improved estimation of timestep for Martini systems [2022-4]
• MD Multistage: Option to concatenate stages together for speed-up [2022-4]
• MD Multistage: Built-in Martini relaxation protocol suitable for NVT ensemble [2022-4]
• MD Multistage: Option to only write out selected molecules to trajectories (command line) [2022-4]
• Stress Strain: Output CSV updated at each new data point [2022-4]
• Thermophysical Properties: Support for Parrinello-Rahman barostat (command line) [2022-4]

Quantum Mechanics

• Band Shape: Option to add/select implicit solvent [2022-4]
• Organometallic Conformational Search: Option to select conformers after QM calculations (command line) [2022-4]
• Organometallic Conformational Search: Support for custom MacroModel COM files (command line) [2022-4]
• Organometallic Conformational Search: Support for MOPAC (command line) [2022-4]

Education Content

• Get Going with Materials Science Maestro Video Series added to Documentation [2022-4]
• Quick Reference Sheets available from both Documentation and Training webpages [2022-4]
• New Tutorial: Evaporation [2022-4]
• New Tutorial: Machine Learning Property Prediction [2022-4]
• Updated Tutorial: Polymer Electrolyte Analysis [2022-4]
• Updated Tutorial: Computing Atomic Charges [2022-4]
• Updated Tutorial: Activation Energies for Reactivity in Solids and on Surfaces [2022-4]
• Updated Tutorial: Organometallic Complexes [2022-4]

LiveDesign

What’s new in LiveDesign 2022-4

• The number of logins is enforced by a license limit: Users who attempt to log in after the number of available seats have been assigned will be denied access to LiveDesign
• Admins can forcibly log out users: Users can be forcibly logged out by removing their assigned Roles, or by specifying a specific username
• File Import Receipt: Receive feedback on file imports when the file contains errors, and instructions on how to correct the errors
• Sketcher Improvements:
  • Implicit mode sketcher: Quickly switch between editing compounds and selecting a subset of the compound, by clicking directly on the select tools and draw tools
  • Delete an atom by hovering over it and pressing the Backspace key on the keyboard
• Setting a protocol’s parameter to “Set Default” in the admin panel changes all existing models’ parameter to “Set Fixed”
• Interaction Surface within LigandDesigner: view the interaction surface to determine available growth space within a binding pocket
• Copying a single compound from the spreadsheet can be copied in a Mol v3000 format: a server wide setting permits copying a single molecule as either Extended SMILES or Mol v3000. Selecting and copying multiple compounds as once will copy the compounds using a SMILES format
• Freeform column picklist options can be reordered: Editing a Freeform column definition permits reordering the picklist options
• UI Improvements
  • View more tiles on screen in Tile View, which has a much smaller tile size limit
  • View more data in a spreadsheet cell; the “More Available…” message within spreadsheet cells has been replaced with a gradient to indicate additional data is in the cell
  • Users can use Ctrl-Click to easily display results from additional 3D models in the 3D visualizer.
  • Exported compound structure images will now include stereochemistry labels if these are turned on in the spreadsheet.

What’s Been Fixed

• Model columns can now be sorted and filtered when the cell contains both blank values and numeric or string values. Sorting will use the first non-empty value in the cell.
• Advanced searches with multiple Freeform column conditions return the same results even if the condition order is changed
• Compound images no longer show large atom labels when clicking on them within the main spreadsheet
• Project admins can edit all formulas within their projects
• Pinned plot tooltips in the visualize panel will reappear even after switching to another plot or another LiveReport
• Deleted LiveReports cannot be reopened by navigating directly to the LiveReport’s URL
• Pinned plot tooltips in forms update the connecting line when the view is resized
• Pasting multiple values into Filters will, once again, attempt to automatically identify the delimiter, or present an option to select the delimiter, by which to separate values.
• The LiveReport Manager dialog no longer obscures the last LiveReport with a horizontal scroll bar
• Bond angles for attachment points and carbon atoms from R-group decompositions are now displayed as angles of less than 180 degrees, while before they were displayed at a 180 degree angle
• LiveReports with 3D model returns no longer show a red error bar after opening
• Commons-text has been upgraded to patch security vulnerability CVE-2022-42889
• The 3D visualizer uses the high performance GPU on client computers to avoid crashes
• Formula results no longer disappear from the spreadsheet when columns used in the formula are hidden in the LiveReport
• The matched molecular pairs tool no longer fails to parse chiral compounds represented in an Extended SMILES format
• Error messages no longer sporadically appear when models are updated and saved in the Admin Panel

Small Molecule Drug Discovery

Target Validation & Structure Enablement

Protein Preparation

• Reorganized and grouped Protein Prepwizard command line options for improved clarity and correspondence with the Maestro interface [2022-3]
• Improved valence error reporting in Diagnostics interface [2022-3]
• Several orders of magnitude speedup when assigning zero-order bonds and running the Epik stage in the Protein Prepwizard on large structures such as a ribosome [2022-3]
• Several times faster performance of ProtAssign when running on large structures with many small clusters or structures with a few large clusters [2022-3]
• Addition of -include_ligand_states flag in command line prepwizard and protassign scripts, to include Epik generated ligand states during the hydrogen bond assignment stage [2022-3]

Protein X-Ray Refinement

• Phenix/OPLS: Option to significantly improve computational performance by lowering the nonbonded energy term cutoff [2022-3]
  • A Phenix-side option schrodinger.flags.nonbonded_cutoff changes the cutoff. Default is to not change the cutoff. This has been tested with a cutoff of 10 angstrom, which increases computational efficiency by several times while no penalty to refinement statistics is observed.

Cryo-EM Model Refinement

• Introduced a new mode peptide for GlideEM, for enhanced peptide sampling with the command line parameter -nconformers specifying the number of conformers to generate [2022-3]
  • Additional input conformations are generated by running confgen on the peptide and redocking each conformation. The time and required computational resources required scale linearly with -nconformers
• Binding pocket / docking grid center can now be specified by binding site ASL and the ligand provided in a separate file in GlideEM [2022-3]
  • The binding site can be specified using the new -binding_site_asl command line argument, which requires an ASL that specifies residues near the binding site. The docking grid center will be the geometric mean of all atoms specified by the ASL. The ligand can be provided using the -ligand_struct command line argument

Platform Environment

Maestro Graphical Interface

• Apply styling and change molecular representations on selected entries [2022-3]
• New Workflow Action Menu support for Protein-Protein Docking [2022-3]
• “Send to PyMOL” panel preserves Maestro’s non-bonded interactions when viewed in PyMOL [2022-3]
• Create zero order bonds withing the 2D sketcher [2022-3]
• More reliable selection with improved accuracy of selecting atoms and bonds within the 2D sketcher [2022-3]
• Save user selection of authentication with LiveDesign by either credentials or single sign-on [2022-3]
• New Help icon provides access to relevant tutorials as well as documentation [2022-3]

Force Field

• Improvements to scalability of large FFBuilder jobs [2022-3]

Workflows & Pipelining [KNIME Extensions]

• Schrödinger extensions are compatible with KNIME 4.6 [2022-3]
• Create and apply ML models with new DeepAutoQSAR nodes [2022-3]

Hit Identification & Virtual Screening

ABFEP

• Performance in ABFEP loading [2022-3]

Lead Optimization

FEP+

• Drastically improved interactive performance of FEP+ Analysis tab interface with large maps with 100s of nodes edges [2022-3]
• Correlation plots will show pairwise ddG histogram (previously edgewise was shown) [2022-3]
• State Groupings GUI [2022-3]
  • Tautomers
  • Protomers
  • Conformers (binding poses)

Protein FEP

• Residue Mutation Selection layout change [2022-3]
  • Added support of CYM amino acid (deprotonated Cysteine)

Constant pH Simulations (Beta)

• The pH interval is fixed at 0.5 units and show number of resulting replicas [2022-3]

Solubility FEP

• Experimental ΔG data is shown in Analysis tab if the data is available [2022-3]

Biologics Drug Discovery

• Protein Interaction Analysis
  • Filter protein-protein interaction by residue features, non-bonded interaction types, and interaction distances [2022-3]
  • Buried solvent-accessible surface area and surface complementarity of interface residues reported in results table [2022-3]
  • Select, display and style only interface residues in interaction analysis panel [2022-3]
• Residue Mutation
  • Enhanced performance of residue scanning from Maestro, enabled hundreds of thousands of mutations to be examined simultaneously [2022-3]
  • Mutated residue name added as as property in the residue scanning output structure to facilitate downstream analysis and workflow scripting [2022-3]
• Protein-Protein Docking:
  • Guidance on common next steps provided following PIPER docking through the Workflow Action Menus  [2022-3]
• Antibody Loop Modeling
  • Specify numbering scheme, and thus loop definitions, prior to running PRIME loop refinement including Chothia, Enhanced Chothia, Kabat, IMGT and AHo [2022-3]

Materials Science

GUI for Quantum ESPRESSO

• Effective Screening Medium: Option to align structures in GUI from selected entries [2022-3]
• Quantum ESPRESSO: Support for runner.py to run TDDFPT [2022-3]
• Quantum ESPRESSO: Restart option for ab initio MD (command line) [2022-3]
• Quantum ESPRESSO: Support for slab models with custom dimensionality [2022-3]
• Quantum ESPRESSO: Upgrade to Quantum ESPRESSO 7.1 [2022-3]

Molecular Dynamics

Transport Calculations via MD simulations

• Viscosity: Thermostat and barostat settings (command line) [2022-3]

Coarse-Grained (CG) Molecular Dynamics

• CGFF Builder: Better estimation of particle volume prediction using atomistic structures [2022-3]
• CGFF Builder: Option to set common mass for all particles. [2022-3]
• CGFF Builder: Implicit charges stored in the FF file and reported in the viewer [2022-3]
• CGFF Builder: Option to import saved SMARTS pattern [2022-3]
• CGFF Builder: Default bond-length bounds adjusted by the cutoff [2022-3]
• CGFF Builder: Each CG-mapped molecule type saved as a copy [2022-3]
• Viscosity: Automatic setup of thermostat and barostat for CG systems [2022-3]

Optoelectronics

• AL OptoE: Expanded property space for optimization [2022-3]

Dielectric Properties

• Complex Permittivity: Improved UI to show permittivity for specified frequency [2022-3]
• Complex Permittivity: Separate visualization of storage and loss functions [2022-3]

MS Maestro Builders and Tools

• Nanostructure: Periodicity of the output structures set by default [2022-3]
• Polymer: Template for Chitosan and Xanthan Gum under Carbohydrates [2022-3]
• Polymer: Hydroxyl group as the default terminator for carbohydrates [2022-3]
• Semicrystalline Polymer: Support for running on multiple hosts [2022-3]

Classical Mechanics

• Molecular Deposition: Preview of the number of MD stages [2022-3]
• MD Multistage: Temperature control in brownian stage [2022-3]
• MD Multistage: Relaxation protocol for stiff polymers [2022-3]
• Polymer Crosslink: Option to store and recall SMARTS patterns [2022-3]
• Polymer Crosslink: Option for SMARTS search method (command line) [2022-3]
• Stress Strain: Option for SMARTS search method (command line) [2022-3]
• Stress Strain: Speed up (up to 2x) of cyclic stress strain jobs [2022-3]
• Stress Strain: Preview of total simulation time from the GUI [2022-3]
• Surface Tension: Support for long-range cut-off [2022-3]
• Surfactant Tilt: Improved UI for surfactant selection [2022-3]
• Trajectory Density Analysis: Improved UI for trajectory range setup [2022-3]

Quantum Mechanics

• Adsorption Enumeration: Option to position adsorbate distanced from the substrate [2022-3]
• Excited State Analysis: Support for custom definition of fragment [2022-3]
• QM Multistage: Option to turn off robust convergence [2022-3]
• Ligand Exchange: Report of detailed progress in the driver log [2022-3]
• Automatic spin treatment as default for Jaguar Options within QM panels [2022-3]
• Reaction Workflow: Support for geometry deduplication [2022-3]
• Reaction Workflow: Support for η- or centroid- representation for output [2022-3]
• Reaction Workflow: Support for specifying R-group enumeration sites [2022-3]

LiveDesign

What’s new in LiveDesign 2022-3

• Machine Learning: Predict properties by building and using DeepAutoQSAR and a model management tool
• Kanban layouts: Visualize and manage workflows, projects, and synthesis queues
• View all assay data for a compound: Query all assay data for a compound by using the Assay Data Viewer tool
• Matched Molecular Pairs: Perform a matched molecular pairs analysis by querying precomputed datasets or generating analyses on-the-fly, and analyze multiple properties at once
• New enhancements to existing features, such as:
  • Configure models to use options from a picklist
  • Plot multiple experimental values for a single compound
  • Updated plot legend that no longer overlays the plot
  • View drop down suggestions that are specific to the LiveReport in Filters, Coloring Rules dialogs, and MPO Configuration dialogs
  • Switch modes in the Sketcher by using the keyboard’s spacebar
  • Ligand Designer allows for more simultaneous users due to more rapid license checkout and return
  • Compound images show heteroatoms that are proportional to bond lengths
  • Hide tabs on Forms widgets to improve screen real estate usage
  • Updated tooltips for experimental values, which can open the Assay Viewer tool to inspect experimental metadata
  • Automatically generate coloring rules based on row selection for categorical columns
• New performance improvements that speed up advanced search, speed up sorting, and speed scrolling in LiveReports with many columns
• Workflows & Pipelining [KNIME Extensions]
  • When deploying a model the suitable KNIME protocol is chosen automatically and the latest version of the protocol uploaded
  • Distribution of calculations is controlled from the model admin page
  • Model changes from the LiveDesign Admin page can be preserved when overwriting an existing model
  • A new administration node to move, archive and unarchive models

What’s been fixed

• Column tree search terms and results are now resetting upon clicking cancel on a dialog and accessing again.
• Tile View header names  for unpublished columns use a hash background for the entire cell, while before it was only used for the text itself.
• A format inconsistency when a Tile includes a 3D column has been fixed.
• The “Unfreeze all rows” message now disappears once clicked from other views than spreadsheet, while before it was persisting.
• Global templates can now be applied to an existing LiveReport.
• The display of the tooltip of the Save button for Landing Page bookmarks has been fixed.
• In the LiveReport picker, selection is now kept if the creation of a new folder is aborted.
• LiveReports including MPO can now be copied to other projects.
• Project picker does not persist anymore if a user navigates to a LiveReport using its URL.
• Date field values of Landing Page bookmarks are now validated. An incorrect value will trigger a warning message.
• Template search on Landing Page is now case insensitive.
• MPO tooltip now properly displays all constituents information even for constituents not present in the current view.
• MPO tooltip position was not consistent depending on the presence of a proxy value score. It now is.
• MPO score now appropriately reflects the change of a previously defined constituent that is changed to a null value.
• Legend now pops out with a chart when not attached.
• Plot legend is now appropriately repositioned upon screen resolution changes.
• Box Plots now supports a larger number of data points.
• Export to image of line plots split by series with a large amount of data now include all data points as expected.
• Histogram and Pie plot tooltips now show decimal separators as per the server setting.
• In the Firefox browser, user axis font size is now taken in account while it was ignored before.
• The warning message indicating that the number of allowed points in a plot has been exceeded is now properly displayed. In particular it is not hidden anymore by the message offering to activate Jitter functionality in scatter plots.
• When exporting plots to images, data points now have borders, preventing points without color to not be displayed in the image.
• Sgroup annotations of abbreviated functional groups for structure imported in v2000 CTAB format are now properly displayed.
• The property RDKIT_STRUCTURE_PROCESSOR_SGROUP_FIELD_NAMES, which defines which Sgroup fields should be considered as part of registration, is now properly taken in account.
• R-group Decomposition now matches tautomers when “RDKIT_TAUTOMER_SEARCH” is set to true.
• First click on the sketcher now focuses the input, while before it was adding a CH4 to the sketch.
• Fix an issue impacting the sketcher display after successive change of the size and/or minimization of the browser window.
• Upon upgrade, the new version of the sketcher does not require a hard refresh of the page orto clear the browser cache.
• Dragging a compound into the sketcher, and then adding a ring or bond, will show a proportionally sized ring or bond.
• Advanced searches with an inverted “Presence in LiveReport” now return results.
• Freeform columns that are hidden in the LiveReport now appear as options for the Kanban widget.
• The kanban widget now shows tiles in edit mode after configuring the widget.
• R-groups can now be added to the LiveReport via the sketcher.
• Uploading unpublished data from Maestro, and then re-uploading that data as published to the same LiveReport, now shows those columns in the Data & Columns tree.
• Hidden columns now appear in the file export when they are explicitly selected.