Download Schrodinger Suites 2026-2 x64 Windows/Linux/macOS

Platform Environment

Maestro Graphical Interface
– Interactive 2D Overlay: Precision marquee and lasso selection on the 2D Overlay that synchronizes instantly to the Workspace, bypassing the visual clutter of the 3D binding site.
– Task Tool Smart Search: Intelligent, fuzzy search that understands user intent – instantly locating the desired panels even with typos or conceptual queries like ‘dockng’ or ‘T-cell’
– Maestro Assistant:
. Agentic Status Indicators: Real-time status updates replace the generic loading animation, so you always know what the assistant is doing.
. Multiple persistent chat sessions – Users can now create, rename, switch between, and delete multiple chat sessions, each maintaining its own conversation history.
. Privacy & Transparency Controls: Users can now enable or disable the Maestro Assistant directly from Preferences, with clear in-UI communication of the current privacy mode. The updated welcome screen and persistent AI disclaimer footer reinforce that your workspace structures are never sent to the LLM.
– Surfaces: Projecting ESP and Fukui reactivity maps onto Jaguar-computed electron density isosurfaces is now a single-click action, where previously it required multiple manual steps.
Force Field
– Improvement in the accuracy of metal complexes and metal-ligand interactions of specific metal ions (Ca(II), Mg(II), Fe(II), Zn(II), Pt(II), Ir(III)) from the addition of the metals polarizable force field via OPLS5. Current application support is in relative/absolute binding FEP+ and Desmond (beta).

Target Validation & Structure Enablement

Protein Preparation
– Improved ease of use to assess clashes with crystal mates in the Diagnostics panel
– New and improved side-chain reconstruction algorithm
– Better logging of use and matching of FASTA sequences to entry
– Academic Maestro can now minimize prepared structures
– Automatically fix bonding of sulfoximines, which are often incorrectly assigned in the wwPDB/CCD
– New option to automatically add glycosylation bonds in Maestro
– Detect ring spears during preprocessing, displaying them in the ‘Overlapping’ Diagnostic pane
Predictive Tox Panel
– Full release of the Predictive Tox panel for screening unknown liabilities
– Open beta release of the Predictive Tox SAR panel for automated production of high accuracy atomistic models of common anti-targets using existing SAR

Binding Site & Structure Analysis

Mixed Solvent MD (MxMD)
– Save a manual step with automatic execution of SiteMap rescoring as part of MxMD simulations
– Density maps are now written in ccp4 format instead of cns

Hit Identification & Virtual Screening

Docking
– The high-accuracy MacroDock macrocycle docking workflow is now available from the command line
– Enhanced performance and efficiency in ultra-large library screening with Generative Glide (Beta): Efficiently screen ultra-large on-demand synthesizable libraries with generative AI in a fraction of the time as AL-Glide and brute force approaches

Ligand Preparation

Enumeration
– New interface to enumerate novel molecules using generative AI for molecular materials with the REINVENT method
Shape Screening
– QuickShape now stores oned_screen results as .csv
ABFEP
– Apply restraints from the interface

Lead Optimization

FEP+
– Identify the optimal simulation time to maintain accuracy with time-sliced statistics
– Share FEP+ protocols across Web Services (GraphDB), Active Learning FEP, and the FEP+ Protocol Builder for consistency with easy import and export of new FEP+ protocol configuration files
– Improved Force Field parameter merging
– Improved cycle-closure calculation performance by up to 100x by saving subcycles and graph traversal
Protein FEP
– Renamed protein “selectivity” to “affinity” to be consistent with residue scanning
FEP+ Protocol Builder
– Account for “grouped” compounds when assigning test/train splits
Macrocycles
– Macrocycle Score: New semi-automated workflow to optimize and score macrocyclic cores for a given set of conformers, with support for high-fidelity scoring with MLFFs and QM
– Macrocycle Stability: New script for using binding pose metadynamics to rank macrocyclizations for stability compared to a reference molecule
– Macrocyclize: More detailed rejection reasons are now reported for cyclization reactions
– Macrocyclize: Automated enumeration of all L- and D-amino acid attachment pairs for custom SMILES linkers in peptide mode
– Prime Macrocycle Sampling: New command-line argument, -use_random_seed, to set a random seed during sampling
– Prime Macrocycle Sampling: New command-line argument, -curvature_tol, to specify curvature restraints during sampling
– Prime Macrocycle Sampling: New command-line argument, -freeze_torsions, to specify torsions to freeze during sampling

De Novo Design

AutoDesigner – R-group Design
– Full release of R-group Design panel
– Improved AutoDesigner PDF report
AutoDesigner – Core Design
– Full release of Core Design panel
– Improved AutoDesigner PDF report
AutoDesigner – Linker Design
– Full release of Linker Design panel
– Improved AutoDesigner PDF report

Drug Formulations
– Formulation ML: Support for proteins
Crystal Structure Prediction
– Full release of Crystal Structure Prediction with support of anhydrous Z’=2 and monohydrate crystal polymorph structures: Identify stable crystal polymorphs at zero Kelvin and room temperature for a given compound through hierarchical scoring

Docs Content
– Filter tutorials based on interest
– Materials Science Panel Explorer URLs retain filter states
– New interactive GPU licensing calculator
– Collapsible sidebar menu

Education Content
– New Tutorial: Filtering and Validating Protein-Protein Docked Poses with Macromolecular Pose Filtering and MM-GBSA Residue Scanning
– New Tutorial: Introduction to Performing Metadynamics Simulations with Desmond
– New Tutorial: Screening Ultra-large Libraries with Generative Glide
– New Tutorial: Peptide Cyclization
– New Tutorial: Preparing Cyclic Peptides and Aligning them to a Reference Structure
– New Interactive Tutorials: Three interactive tutorials for AutoDesigner, a de novo design algorithm for rapidly exploring large chemical space for lead optimization
. Set up Linker Design with AutoDesigner in Maestro
. Set up Core Design with AutoDesigner in Maestro
. Set up R-Group Design with AutoDesigner in Maestro

Biologics Drug Discovery
– Non-standard amino acids script (Open Beta). A command line script to simplify and speed creation of non-standard amino acid databases for residue scanning.
– Introduced a “Fast Mode” command line option for calculating protein descriptors. The new mode speeds up computation of these descriptors by about 20% on a benchmark dataset. Especially useful for large ensembles of structures.
– Enabled light-chain template subtype selection during antibody modeling. This provides greater flexibility when selecting templates for generating antibody structural models.
– Added the lengths of antibody Complementarity-Determining Regions (CDRs) to the output of calculated protein descriptors for antibody profiling analyses.

GUI for Quantum ESPRESSO
Product: Quantum ESPRESSO (QE) Interface
– Reduced disk space usage for calculating partial charges
– Bader charge analysis (command line, requires Badar module installation)
– Parallelization over both bands and tasks (command line)
– Support for MLFF in NEB calculations
Defect Properties:
Product: MS DefectPro
– Defect Formation Energy Diagram: Analysis panel for defect energy
Microkinetics
Product: MS Microkinetics
– Improved UI for renaming reactions
– User control of displayed stage in the Final State tab
Active Learning Optoelectronics
Product: Active Learning Optoelectronics
– (+MATSCI_OPTO_AL_ML) Access to ML property prediction models
– Prediction for fluorescence
Reactivity
Product: MS Reactivity
– Reaction Network Viewer: Color scheme to identify reactants
– Nanoreactor: Setup for number of stored structures to calculate biasing potential (command line)
– Nanoreactor: Improved sampling of input conformations
– Nanoreactor: Option to use AutoTS for transition state analysis
Crystal Structure Prediction
Product: Crystal Structure Prediction
– Crystal Structure Prediction: Support for Z’=2 and monohydrates
Advanced Force Field Applications
Product: MS FF Applications
– Infrastructure: Support for metals with OPLS5 from the materials science workflows (open beta)
Transport Calculations via MD simulations
Product: MS Transport
– Diffusion Coefficient: Support for multi-component diffusion analysis
– Ionic Conductivity: Output report in the driver log for command-line access
– Thin Plane Shear: Support for viscosity prediction from velocity profile
Coarse-Grained (CG) Molecular Dynamics
Product: MS CG
– Coarse-Grained Mapping: Standardized color scheme for Martini protein residues
– Backmapping: (+COARSE_GRAIN_BACKMAPPING) Algorithm to map coarse-grained structures to all-atom models
– Coarse-Grained FF Assignment: Automatic setup of restraints for DPD mapping
– CG FF Builder: (+CGFF_BUILDER_PARAM_NO_RESPONSE) Improvements to fitting algorithms for bond and angle terms
– CG FF Builder: Martini type guesses made visible to users
– Particle and residue names visible in MS Maestro
– Improved Martini parameters for linear polysaccharides
Complex Bilayer Builder
Product: MS Complex Bilayer Builder
– Membrane Analysis: Automated head/tail assignment independent of pdb names
Formulation ML
Product: MS Formulation ML
– Formulation ML: Support for protein
– Formulation ML: Support for aggregation functions over ingredient descriptors
Layered Device ML
Product: MS Layered Device ML
– Support for using existing device models as descriptors for new device models
Generative AI
Product: MS Generative AI
– REINVENT: Generative AI for molecular materials using the REINVENT method
MS Maestro Builders and Tools
– Disordered System: Support for barrier potential with planar interface substrates
– Interface Builder: (+INTERFACE_BUILDER) Advanced solution for building interface models
– Materials Project: API key from materialsproject.org hidden from the panel UI
– Meta Workflows: Support for order parameter analysis
– Meta Workflows: Support for bulk macromolecule relaxation protocol
– Periodic Structure Enumeration: Option to rank by electrostatic energy
– Polymer: Speed-up for building ladder polymers
– Remove Molecules from System: Speed up of up to 100X for loading CG systems
– MD Multistage: Improvements to built-in relaxation protocol ‘Semicrystalline 1’
– Solvate System: Option to prevent molecular splits across periodic boundaries
– Sugar Builder: Stand-alone model building solution for common polysaccharides
Classical Mechanics
– Droplet: Coarse-grained structures enabled
– Electrolyte Analysis: Support for 2D distribution analysis of coordinating shells
– Electrolyte Analysis: Support for cluster composition analysis
– Electrolyte Analysis: Support for residence time analysis
– Electrolyte Analysis: A tab in the viewer panel to summarize analysis results
– Electrolyte Analysis: Display of RDF and structure factor plots
– Polymer Crosslink: Support for NpγT and NpAT ensembles
– Polymer Crosslink: Support for opening multiple viewer windows
– Surface Tension: (+SURFACE_TENSION_CG) Support for coarse-grained models
– Thermophysical Properties: Option to stop after a series of failed simulations
– Thermophysical Properties: Support for varying MD timesteps by temperature
– Thermophysical Properties: Display of Calibrated Tg value from the viewer panel
– Thermophysical Properties: Support for MLFF
– Umbrella Sampling: Option to export potential of mean force to CSV output
Quantum Mechanics
– Adsorption Energy: Atomic constraints setup for molecular QM calculations
– Adsorption Energy: Improved interface for setting atomic constraints
– Optoelectronic Film Properties: Option to select the excited states of interest for ISC/RISC
– Optoelectronic Film Properties: Improved parallelization for ISC/RISC
– Optoelectronic Film Properties: Geometry optimization settings for ISC/RISC
Docs Content
– Filter tutorials based on interest
– Materials Science Panel Explorer URLs retain filter states
– New interactive GPU licensing calculator
– Collapsible sidebar menu
Education Content
– New Tutorial: Protein Characterization: Part 1
– New Tutorial: De Novo Design of Novel Compounds with REINVENT
– New Tutorial: Machine Learning for Formulation Containing Proteins
– Updated Tutorial: Droplet Contact Analysis
– Updated Tutorial: Nanoreactor
– Updated Tutorial: Liquid Electrolyte Properties: Part 2
– Updated Tutorial: Defect Formation Energy Calculation
– Updated Tutorial: Crystal Structure Prediction
– Quick Reference Sheet: Sugar Builder

Platform Environment

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

Binding Site & Structure Analysis

Mixed Solvent MD (MxMD)
– Added support to command line MxMD driver to seamlessly execute all simulations and compile results from combined MxMD/SiteMap cryptic pocket identification workflow
WaterMap
– WaterMap now supports use of the OPLS_2005 forcefield and TIP4P water model

Hit Identification & Virtual Screening

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

Lead Optimization

FEP+
– GraphDB/Web services can optionally download only the primary FMP file and not the FMPdb reducing time to analyzing results
– FEP+ workflows now support execution on cost-effective preemptible nodes
– Use 2D Sketcher to define Core SMARTS for FEP+
– Improved handling of categorical assay data in FEP+ statistical analysis
FEP+ Protocol Builder
– Sample three levels of salt concentrations in protocol optimization
– Sample automatic membrane placement in protocol optimization
FEP+ Pose Builder
– Automatically create accurate and clash-aware FEP-ready poses with FEP+ Pose Builder: Generate high-quality ligand alignments faster to run FEP+ at scale with an automated workflow designed for unbiased selection and robust atom-mapping
– LiveDesign FEP+ Pose Builder protocol now supports generating FMP files for cycle-closure FEP calculations
Quantum Mechanics
– Employ xTB and MLFFs including QRNN, MPNICE, and UMA in AutoTS from command line for shorter calculation times
– Faster batch calculations by optimized CPU core assignments for all multithreaded Jaguar batch calculations
Spectroscopy
– New corrections for C-Br and C-I bonds in 13C NMR spectra

De Novo Design

AutoDesigner – R-group Design
– Explore large chemical spaces to identify optimal R-groups with new AutoDesigner R-group Design Panel now accessible by setting a feature flag
– Added optional QED score (Quantitative Estimate of Drug-Likeness) for AutoDesigner R-group Design ideas
AutoDesigner – Core Design
– Explore large chemical spaces to identify optimal core replacements with new AutoDesigner Core Design Panel now accessible by setting a feature flag
– Added optional QED score (Quantitative Estimate of Drug-Likeness) for AutoDesigner Core Design ideas
Education Content
– Introducing a new, more interactive tutorial experience, letting users intuitively click through the steps of a workflow right in the tutorial. This approach is being piloted in two tutorials.
. Updated Tutorial: Structure-Based Virtual Screening Using Glide
. Updated Tutorial: Introduction to Structure Preparation and Visualization
– Fully re-worked learning content on Antibody Modeling:
– The “Antibody Visualization and Modeling in BioLuminate” tutorial has been replaced by a new suite of tutorials organized in a learning path together with other helpful resources.
. New Learning Path: Antibody Modeling
. New Tutorial: Antibody Structure Prediction and Visualization with BioLuminate
. New Tutorial: Humanizing Antibody Structures with BioLuminate
. New Tutorial: Antibody – Antigen Docking with PIPER
. New Tutorial: Improving Antibody Stability/Affinity Using MM-GBSA Residue Scanning
– New Tutorial: Generating ternary complex structures to enable rational design of targeted protein degraders
– Updated Tutorial: BACE1 Inhibitor Design Using Free Energy Perturbation
– New Quick Reference Sheet: Force Field Builder
– New Quick Reference Sheet: Ligand Interaction Diagram

Biologics Drug Discovery

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

GUI for Quantum ESPRESSO
Product: Quantum ESPRESSO (QE) Interface
– Defect Formation Energy: Workflow solution to analyze point defects in crystals
– Options to set frequency cutoff / harmonic threshold in the Phonon DOS Viewer
– Support for TB09 density functional (command line)
– Support for rVV10-SCAN density functional (command line)
– Support for NpT ensemble in QE BOMD simulations (command line)
– (+MATSCI_NEB_MLFF) MLFF integration in NEB
MS Surface
Product: MS SurfChem
– Desorption Enumeration: WAM to open results in Adsorption Energy
Microkinetics
Product: MS Microkinetics
– Option to view selectivities and degrees of selectivity control
– Option to load/save archived MKM output
– Option to export reaction view as an image (PNG) file
– Results from individual stages made visible from the analysis panel
Optoelectronics Genetic Optimization
Product: Genetic Optimization (GA)
– Support for setting target property based on models from ML Property Prediction
Active Learning Optoelectronics
Product: Active Learning Optoelectronics
– Option to set target values excluded from optimizations
Reactivity
Product: MS Reactivity
– Nanoreactor: Option to specify separate hosts for driver and subjobs
– Nanoreactor: (+NANOREACTOR_AUTOTS) Automatic transition state search for elementary reaction network calculations via AutoTS
– Nanoreactor: Option to skip generating trajectory files
– Nanoreactor: User control over the time interval between trajectory frames
– Reaction Network Profiler: Option to refine conformer geometries using UMA (MLFF)
– Reaction Network Profiler: Option to assign stoichiometric multipliers for reactants
Transport Calculations via MD simulations
Product: MS Transport
– Ionic Conductivity: Support for MLFF
Dielectric properties
Product: MS Dielectric
– Complex Permittivity: Support for multi-component systems
Coarse-Grained (CG) Molecular Dynamics
Product: MS CG
– CG FF Builder: Improved detection and mapping of non-isomorphic residues
– CG FF Builder: Automated particle naming scheme with chemical context
– CG FF Assignment: Up to 15x speed-up for models with a large number of particle types
– Coarse-Grained Mapping: Residue number and name retained through mapping
– Coarse-Grained Mapping: Option to import SMARTS patterns from previous use
– Speed-up for DPD simulations of up to 30% with improved cutoff margins
Complex Bilayer Builder
Product: MS Complex Bilayer Builder
– Complex Bilayer: (+COMPLEX_BILAYER_BUILDER_EXTENDED_LIPID_LIB) Expanded list of default lipids
– Complex Bilayer: Increased limit for water padding depth to 5000 Å
– Complex Bilayer: Support for custom-trained OPLS
– Membrane Analysis: (+MEMBRANE_ANALYSIS_PREP_FOR_FEP) Support for generating poseviewer formatted files compatible with FEP calculations
– Membrane Analysis: Support for applying multiple leaflet-finding algorithms
Materials Informatics
Product: MS Informatics
– Machine Learning Property: Improved panel interface for model selection
– MD Descriptors: User control over simulation system size (max # of atoms)
– MD Descriptors: Support for formulation input with path assigned to structure files
– MLFF Calculations: Option to set constraints to atomic positions
– MLFF Calculations: Support for running on GPU nodes
Formulation ML
Product: MS Formulation ML
– Formulation ML: ‘Learned Fingerprint’ as a new option to feature space
– Formulation ML: Advanced option to process (‘impute’) training set data with partially missing descriptors
– Formulation ML: Improved UI for parity plot
– Formulation ML: Support for building machine learning models using training datasets with missing chemical (SMILES) information
– Formulation ML: Target property displayed in the ‘Performance’ tab
– Formulation ML: User control over correlation threshold between features
– Formulation ML Optimization: Support for custom-ingredient descriptors
– Formulation ML Optimization: Support for multi-CPU parallelization
– Formulation ML Optimization: Option to use genetic algorithms for formulation optimization
Layered Device ML
Product: MS Layered Device ML
– OLED Device ML: User control over correlation threshold between features
– OLED Device ML: Target property displayed in the ‘Performance’ tab

MS Maestro Builders and Tools

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

Classical Mechanics

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

Quantum Mechanics

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

Education Content

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

Education Content

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

LiveDesign

What’s Upcoming in 2026-1
– Design new biologics by using a new Residue Mutation tool to perform single point mutations
– Report on project status with customizable Project Dashboards
– Interact with LiveDesign using an AI Assistant, available with the LiveDesign ML add-on

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

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
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
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

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
Documentation Content
– Licensing information displayed in panel help documentation
– Materials Science Panel Explorer: Filter for panels that support MLFF

LiveDesign

What’s Upcoming in 2025-3
– Upload 3D files into a Freeform column cell and view the structure in the 3D visualizer: View and run parameterizable models on custom 3D inputs
– Overwrite and append file-uploaded data on Biologics: Track and register entities while sequencing

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

– 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

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

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

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 upcoming in 2025-1
– Extended support for biologics drug discovery: Synchronous selection between Sequence Viewer and 3D Visualizer, support for biologic entities in models which expect atomistic representation, and enhancements for handling non-canonical monomers throughout the application
– Data import performance improvements: Faster small molecule file import and large enumeration result import
– Enhanced formula capabilities: Support multiple value inputs to a formula and align multiple value outputs from a formula by experiment, lot, or pose

Small Molecule Drug Discovery

Platform EnvironmentTarget

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 upcoming in 2024-4
– Biologics SAR Visualization: View, highlight, and analyze properties alongside sequence differences in the Sequence Viewer tool
– Ligand Designer: Upload multiple overlays and rename docked poses for tracking
– R-group enumeration: Filter output products by computed properties to enumerate a set of products within a defined chemical space
– Updated LiveReport Picker: View row, column, and cell count for LiveReports in the LiveReport Picker to quickly identify LiveReports that are candidates for deletion

• – 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

• – 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

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

• – 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

• – Improved organization of output structures and data in prjzip file

• – 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)

• – Filter chemotypes by SMARTS in Hit Analyzer Panel

• – 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

• – 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

• – Expanded OPLS5 support for Solubility FEP simulations

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

• – 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

• 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

• – Diffusion: Support for non-orthorhombic systems as input

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

• – 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

• – 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

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

• – 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

• – 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

• – 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

• – 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

• 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

• New OPLS5 Force Field: Significant improvement in the accuracy of cation-pi interactions and polarizable and ionic group interactions via the addition of limited polarizability via OPLS5 in relative binding-FEP+ and Desmond (beta)

• 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

• 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

• 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

• 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

• Ability to export sequences and annotations to seqD file

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

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

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

• Mutation generation will now ignore water molecules for sidechain placement

• 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

• 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

• 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 detailsed patch characteristics in Protein Patch calculations
• Easily perform detailsed analysis of residue scanning results with new csv file containing mutant descriptions and energies

• 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

• 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

• 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

• 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 Keq

• Workflow module for microkinetic modeling of chemical reaction rates

• 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

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

• TST Rate: Jobs launched to queue

• 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