Schrodinger Suites 2025-4

Platform Environment

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

Binding Site & Structure Analysis

SiteMap
- SiteMap now evaluates more sites than requested, returning the requested number of top-scoring sites by SiteScore
Desmond Molecular Dynamics
- Energy Decomposition Analysis panel now supports trajectories generated using custom force field parameters
Mixed Solvent MD (MxMD)
- Addition of immiscible probes in Mixed Solvent MD to better identify cryptic pockets: Use hydrophobic probes to stabilize transiently exposed pockets in an open conformation to increase their residence time and facilitate cryptic binding site identification

Ligand Preparation

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

Lead Optimization

Ligand alignment
- Non macrocycle alignment jobs can run as interactive tasks without submitting a job
Enumeration
- Return only Pathfinder retrosynthetic routes that include purchasable starting materials
FEP+
- Added ligand atomic RMSF analysis for RE-FEP calculations
FEP Protocol Builder
- Enable separate solvent and complex hot atom rules including None
- Enable sampling between OPLS4 and OPLS5 with the new Force Field version parameter
Quantum Mechanics
- Predict optical rotation as a function of wavelength
- Added support for 18 new double hybrid functionals
- Faster simulations with optimized CPU assignments for unbalanced batch jobs and workflows
- Employ QRNN, MPNICE and UMA MLFFs from Jaguar interfaces

Medical Chemistry Design

Ligand Designer
- Interactive Core Hopping: A new Core Swap workflow supports non-ring cores and enables true core hopping transformations, allowing for the exploration of diverse chemical space directly within an interactive design environment.
- Manual attachment point selection for macrocyclization: The newly renamed Macrocyclization workflow allows for the interactive selection of attachment points, providing precise chemical control that focuses linker enumeration on synthetically relevant designs.
De Novo Design
- New PDF report for AutoDesigner workflows to record input settings and summarize enumeration and filtering results

Drug Formulations

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

Alternative Modalities

Bifunctional Degraders
- Optionally build linkers between the two warheads in both directions when using the “Linkers only” option in the Generate Degrader Ternary Complexes interface
- Prioritize ternary complexes for linker design with a new interface to score degrader ternary complexes powered by a validated Metadynamics-based workflow (beta)
Education Content
- New Learning Path: T Cell Receptor Engineering
- New Tutorial: Enzyme Engineering with BioLuminate
- Updated Tutorial: Validating a Protein Free Energy Perturbation Model for Thermostability Predictions for Single Point Mutations (previously “Obtaining Protein Free Energy Perturbation Thermostability Predictions for Single Point Mutations”)
- Updated Tutorial: Improving the Thermostability of T4 Lysozyme Using Protein FEP+ Guided Design (previously “Introduction to Protein Thermostability Prediction using Protein FEP+”)
- Updated Tutorial: Ligand Binding Pose Generation for FEP+ (previously Ligand Binding Pose Prediction for FEP+ using Core-Constrained Docking)
- Updated Tutorial: Structure-Based Virtual Screening using Glide


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

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

MS Surface
Product: MS SurfChem
- Desorption Enumeration: Active entry shown in the workspace
- Desorption Enumeration: Support for enumerating associate desorption products

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

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

Advanced Force Field Applications
Product: MS FF Applications
- Expanded support for MLFF selections in QM- and MD-based workflow solutions
- UMA (developed by Meta Platforms Inc.) added as MLFF option in QM-based workflows
- (+ENABLE_GRPC_MLFF_DESMOND) UMA (developed by Meta Platforms Inc.) added as MLFF option in MD-based workflows

Transport Calculations via MD simulations
Product: MS Transport
- Ionic Conductivity: Workflow solution to predict ionic conductivity in liquid electrolyte systems
- Viscosity: Option to turn off the SHAKE algorithm (command line)
- Viscosity: Support for MLFF

Coarse-Grained (CG) Molecular Dynamics

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

Complex Bilayer Builder

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

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

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

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

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

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

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

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

Education Content

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

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