Release Notes

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.