Release Notes

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

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

Force Field

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

Target Validation & Structure Enablement

Protein Preparation

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

Protein X-Ray Refinement

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

Cryo-EM Model Refinement

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

IFD-MD

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

Binding Site & Structure Analysis

Mixed Solvent MD (MxMD)

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

Hit Identification & Virtual Screening

Docking

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

Ligand Preparation

Macrocycles

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

ABFEP

• Automatic membrane placement for AB-FEP simulations

Lead Optimization

FEP+

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

Constant pH Simulations

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

FEP Protocol Builder

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

Quantum Mechanics

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

Life Science Education Content

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

Biologics Drug Discovery

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

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

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

MS Surface

Product: MS SurfChem

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

Microkinetics

Product: MS Microkinetics

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

Reactivity

Product: MS Reactivity

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

KMC Charge Mobility

Product: MS Mobility

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

Dielectric properties

Product: MS Dielectric

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

Reactive Interface Simulator

Product: MS RIS

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

Crystal Structure Prediction

Product: Crystal Structure Prediction

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

Advanced Force Field Applications

Product: MS FF Applications

• Machine learning force field support in QM and MD panels

Transport Calculations via MD simulations

Product: MS Transport

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

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

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

Materials Informatics

Product: MS Informatics

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

Formulation ML

Product: MS Formulation ML

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

Layered Device ML

Product: MS Layered Device ML

• OLED Device ML: Support for classification models

MS Maestro Builders and Tools

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

Classical Mechanics

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

Quantum Mechanics

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

Materials Science Education Content

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

Education Content

Life Science

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

Materials Science

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

LiveDesign

What’s New in 2025-3

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

What’s Been Fixed

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