Release Notes

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Added nonstandard nucleotide support: Right-click any DNA or RNA residue to mutate it to a nonstandard nucleotide via a searchable panel with 2D structure preview
• New GPCR Workspace Preset for annotated G protein-coupled receptor visualization
• Revamped surface management including comparison of multiple surfaces in the surface toggle: Select multiple surfaces to see a sortable, side-by-side comparison of Area, Isovalue, Sigma, and more in the Info tab. The panel can now be undocked and floated freely
• Simplified Maestro to LiveDesign export for Biologics: Redesigned the Generic Entity export panel (“Biologics/Others”) with two clear workflows, Register New Entities (with HELM-based deduplication) or Append 3D Data to Existing Entities
• Streamlined ability to “Load Selection” for Workspace Interactions: Select atoms in the Workspace, click “Load Selection” in the Interactions dropdown to instantly display their interactions without manually configuring “Other” definitions
• Standalone Map Import in Get PDB: Diffraction data and EM maps are now imported as standalone entries grouped alongside their structures in the Project Table
• New “Other Modalities” Task Tool category with “Degraders” and “Macrocycles” subcategories, grouping specialized panels for easier discoverability
• More intuitive clipping plane zoom controls: The clipping plane view now zooms with the Workspace by default, and new right-click menu options let you toggle clipping plane behavior without navigating to Preferences
• Redesigned Preferences Directories page: Cleaner layout with Browse buttons, clearer terminology, automatic detection of SCHRODINGER_TEMP_PROJECT overrides, and Windows-only sections hidden on Mac/Linux
• “Check for update” option added to the Help menu
• Dramatic improvements in the MSV pairwise sequence alignment

Target Validation & Structure Enablement

Protein Preparation

• Annotate GPCRs automatically during structure preparation
• Selenomethionines are now converted to methionines by default during preparation
• Command-line options overhauled for greater simplicity and to match the Maestro interface’s defaults
• Disable/Hide unusable options in Academic Maestro
• Removed the -noimpref flag from CLI consistent with deprecation of the impref minimization scheme
• Warn users if sidechain atoms could not be rebuilt with the new sidechain rebuilding method

Cofolding

• Maestro panel automatically evaluates and corrects ligand bond orders in prepared models
• Removed confidence based trimming of residues in post-processing
• Full multiple sequence alignment used to construct homology models viewable in the MSV

Predictive Tox Panel

• Added thirteen new GPCR targets to panel, 5HT1B, 5HT2B, 5HT2C, ACM4, ADA2A, ADRB1, ADRB2, APJ, DRD3, OX2R, DRD2, ADORA1 and CNR2
• Added five new bromodomain targets to panel, BRD2 BD1, BRD2 BD2, BRD4, BD1, BRD4 BD2, and CBP
• Added three new nuclear receptor targets to panel, RXRa, AR, ER Beta
• All panel targets supported in both Predictive Tox and Predictive Tox SAR Panels

Binding Site & Structure Analysis

Binding Site Characterization

• First release of Rapid Binding Site Similarity (RBSS)
  • Compute binding site similarities for a protein against all binding sites in the PDB in seconds
  • Compute binding site similarities for a protein against user-provided libraries of binding sites
  • Uses coarsened molecular interaction fields (MIFs) computed on a grid to represent the preference for different functional groups to occupy locations on a grid including, aromatic, hydrophobic, h-bond acceptor, h-bond donor, and positive and negative charges

Desmond Molecular Dynamics

• Speed simulations up to ~66% with support to adjust Hydrogen Mass Repartitioning (HMR)
• Seven new mixed lipid bilayers are now supported by the System Builder

Mixed Solvent MD (MxMD)

• Specify probe target concentration in the input to simulations (command line only)

Hit Identification & Virtual Screening

Active Learning Applications

• Automatically generate the group dG prediction for multi-state protomer groups after including all protonation states of the selected ligands
• Specify the number of lambda windows separately for charged and uncharged ligands for ABFEP and final rescore ABFEP steps
• Apply positional restraints in AL-ABFEP simulations
• AL-FEP+ enriched substructures in the report file now exclude the common core
• AL-ABFEP extends the final rescore ligands instead of running them from scratch to save computation time when ABFEP is run on GraphDB

Docking

• Glide uses ZMQ job distribution (-mq option) by default for faster wall clock turnaround of docking jobs with multiple subjobs through better subjob scheduling

Lead Optimization

RetroSynth

• New combined Maestro RetroSynth setup and analysis panel: Perform and analyze retrosynthesis routes generated by RetroSynth in Maestro or LiveDesign

FEP+

• New ABFEP scanning mode: Perform calculations up to 5x faster with slight loss of accuracy using half lambda windows, 2 ns simulation times, and a truncated receptor
• New Interaction Energy plot fragment decomposition feature: Get a richer understanding of how specific compound fragments interact with the receptor
• Support added for seven new mixed lipid bilayers
• Create “write” submission commands from Maestro interface to Web Services
• PoseBuilder can now generate covalent protein-ligand complex poses ready for covalent FEP+ from command line or in LiveDesign

Protein FEP

• Compute pH-dependent affinities directly from the Maestro interface
• Perform FEP Residue Scanning (FRS) at large scale : New workflow that splits mutations into multiple batches and automatically runs them in parallel before merging results into a single out.fmp file

E-sol

• New panel to setup, execute, and analyze predictions if experimental Efflux ratio data is available

FEP+ Protocol Builder

• Unified Panels that can set up and analyze FEP+ Protocol Builder jobs
• Explore different membrane types as a new parameter
• Command line ‘-prepare’ mode that generates protocols without submitting them

Quantum Mechanics

• Predict compound atropisomerism and analyze key rotational barriers with a new Maestro panel
• Provide an at-a-glance view into the simulation settings and results of an AutoTS calculation in an automatically generated html report

Spectroscopy

• 13C NMR heavy-atom corrections for C-F are now supported

Semi-Empirical Quantum Mechanics

• g-xTB can be invoked from Jaguar after installation by the user (must activate the XTB_GXTB feature flag)

Macrocycles

• New macrocycle docking panel for launching MacroDock jobs
• New sampling options in the Prime macrocycle sampling panel
• Improved macrocycle conformer generation for Glide and IFD-MD docking for ring systems that contain certain nitrogen chemistries
• More thorough sampling of complex multicycles such as vancomycin in Prime macrocycle sampling (Prime-MCS)
• Prime macrocycle sampling (Prime-MCS) conformers are now all automatically aligned to a single reference frame
• Macrocycle docking workflow (MacroDock) is ~2.5x faster than reported in the original publication, reducing the median CPU runtime to under 1 hour per compound while maintaining a success rate of ~80%
• Macrocycle docking workflow (MacroDock) now supports docking with experimental density maps
• New script for batch docking into the same ligand site (macrocycle_batch_docking.py)

Drug Formulations

Crystal Structure Prediction

• Full release of Crystal Structure Prediction supporting salts, solvates, and co-crystals for confident form selection in solid-state development: Computationally screen at scale to identify the most stable, manufacturable crystal form before committing to experiments and secure your formulation strategy

Docs Content

• Learning Paths have been completely redesigned for improved usability

Education Content

• New Learning Path: Cyclic Peptide Modeling
• New Tutorial: Handling Non-standard Amino Acids
• New Tutorial: Modeling Blood-Brain Barrier Penetration Using E-sol
• Redesigned Tutorial: A Chemist’s Guide to Maestro
• Updated Tutorial: Evaluating Large Ligand Libraries with Active Learning Glide
• Updated Tutorial: Introduction to Performing Metadynamics Simulations with Desmond
• New Interactive Mini-tutorial: Rapid Binding Site Similarity Search (embedded in the Panel Help)

Biologics Drug Discovery

• Simple, high-throughput creation of a nonstandard nucleotide library for use in Maestro for DNA/RNA/oliogo design
• New output files from PIPER enables streamlined analysis of docked poses reducing post-processing effort

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Support for dipole correction setup from the input *.cfg file (command line)
• Option to visualize reaction profile as a function of NEB inter-image distance
• Multi-threaded MLFF calculations for NEB calculations (command line)
• GPU support for NEB calculations with MLFF (command line)

Microkinetics

Product: MS Microkinetics

• (+MKM_ELECTROCATALYSIS) Support for multistage workflow for electrocatalysis

Active Learning Optoelectronics

Product: Active Learning Optoelectronics

• Active Learning Optoelectronics: Access to ML property prediction models
• Active Learning Optoelectronics: Access to AutoQSAR/DeepAutoQSAR models

Reactivity

Product: MS Reactivity

• Nanoreactor: Option to adjust biasing potential
• Nanoreactor: Simplified UI for improved user experience
• Nanoreactor: Improved settings for enhanced reaction discovery
• Nanoreactor: AutoTS transition state frequencies reported in the output
• Reaction Network Profiler: Prevention of atom clashes during input preparation

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Improved support for ions with zeroth order bonds

Advanced Force Field Applications

Product: MS FF Applications

• MLFF Fine-tuning: Solution to fine-tune MPNICE MLFF models and use them through in Schrödinger Suite
• MLFF Calculations: Support for vibrations and phonon calculations

Transport Calculations via MD simulations

Product: MS Transport

• Ionic Conductivity: Option to apply linear response theory for predictions
• Thin Plane Shear: Improved definition of plane for shear

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Backmapping: Tool to map coarse-grained systems to atomic representations
• CG FF Assignment: Support for encrypted force field files
• CG FF Builder: Improved selection of data for plotting in viewer
• CG FF Builder: Improved fitting of valence terms
• Coarse-Grained Mapping: Generation of Martini FF file for selected structures
• Visualization of CG protein backbone as tube in the workspace

Materials Informatics

Product: MS Informatics

• MPNICE Embeddings: Machine learning with MPNICE embeddings as descriptor

Layered Device ML

Product: MS Layered Device ML

• OLED Device ML: Option to use pre-trained ML model output as descriptors for new models
• OLED Device ML: Support for tandem OLED devices
• OLED Device ML: Visualization of feature importance from the viewer panel

Denovo ML

Product: MS Denovo ML

• REINVENT: Updated job submission protocol for improved speed

MS Maestro Builders and Tools

• Agentic Workflow: (+MATSCI_AGENTIC_WF) Language-model-based solution to create custom Meta Workflows
• Crystal Structure Prediction: Support for salts and solvents
• Free Volume Analysis: Reduced memory use for the analysis
• Import Slabs: Addition of 25 pre-built slab models
• Interface Builder: Model builder for bulk interfaces and grain boundaries
• Structured Liquid: Redesigned UI for improved user experience
• Sugar Builder: (+NEW_SUGAR_BUILDER_PANEL) Option to build with glycosylation patterns

Classical Mechanics

• Droplet Contact Angle: Support for MLFF
• Electrolyte Analysis: Option to merge neighboring ion clusters for analysis
• Evaporation: Speedup of up to an order of magnitude for coarse-grained systems
• Support for TIP4P water model with OPLS_2005
• MD Multistage: (+MULTISTAGE_MD_CONCATENATE) Option to concatenate Brownie stage with other stages
• Polymer Crosslink: Reduced memory use of free volume analysis
• Thermophysical Properties: Reduced use of disk space

Quantum Mechanics

• Optoelectronic Film Properties: Option to set T1 geometry from DFT or TDDFT
• Optoelectronic Film Properties: Speed up for ISC/RISC reorg energy calculation
• Reaction Network Viewer: Single output for multiple rxn networks (command line)
• Reaction Network Viewer: Option to view structures in the workspace
• Reaction Network Viewer: Option to save reaction network images

Education Content

• New Tutorial: MLFF Fine-Tuning
• New Tutorial: Building Epitaxial Interfaces
• New Tutorial: Protein Characterization: Part 2
• New Tutorial: Machine Learning with MPNICE Embedding
• New Tutorial: Crystal Structure Prediction: Part 2
• Updated Tutorial: Optoelectronics Active Learning
• Updated Tutorial: Ionic Conductivity
• Updated Tutorial: Liquid Electrolyte Properties: Part 2
• Updated Tutorial: Automated Dissipative Particle Dynamics (DPD) Parameterization
• Updated Tutorial: Nanoemulsions with Automated DPD Parameterization
• New Quick Reference Sheet: Coarse-Grained Backmapping

Education Content

Life Science

• New Learning Path: Cyclic Peptide Modeling
• New Tutorial: Handling Non-standard Amino Acids
• New Tutorial: Modeling Blood-Brain Barrier Penetration Using E-sol
• Redesigned Tutorial: A Chemist’s Guide to Maestro
• Updated Tutorial: Evaluating Large Ligand Libraries with Active Learning Glide
• Updated Tutorial: Introduction to Performing Metadynamics Simulations with Desmond
• New Interactive Mini-tutorial: Rapid Binding Site Similarity Search (embedded in the Panel Help)

Materials Science

• New Tutorial: MLFF Fine-Tuning
• New Tutorial: Building Epitaxial Interfaces
• New Tutorial: Protein Characterization: Part 2
• New Tutorial: Machine Learning with MPNICE Embedding
• New Tutorial: Crystal Structure Prediction: Part 2
• Updated Tutorial: Optoelectronics Active Learning
• Updated Tutorial: Ionic Conductivity
• Updated Tutorial: Liquid Electrolyte Properties: Part 2
• Updated Tutorial: Automated Dissipative Particle Dynamics (DPD) Parameterization
• Updated Tutorial: Nanoemulsions with Automated DPD Parameterization
• New Quick Reference Sheet: Coarse-Grained Backmapping

LiveDesign

What’s Upcoming in 2026-3

• Design new antibody-drug conjugates by combining existing antibodies and small molecule linkers and payloads with the Entity Builder tool
• Design new biologics with multi-point and combinatorial residue substitution
• View entities and data in a transposed view with the Multi-Entity Matrix Widget in Forms
• In real-time monitor LiveDesign’s health, task queue length, and performance metrics with the System Health Tool