Release Notes

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Bunsen–Maestro Integration: Launch Maestro and Bunsen from each other’s interfaces and connect active sessions
• Bunsen-Maestro Integration: A new automated modal dialog handler ensures agentic workflows executed in Maestro are never blocked by pop-up dialogs
• High-Scale Maestro to LiveDesign Export Performance: Highly accelerated Maestro to LiveDesign export performance for large datasets; For ~75k compounds time was reduced from about an hour to under 4 minutes
• Polymer-Aware Residue Grouping in the Structure Hierarchy: Non-standard and modified residues within polymer chains are now grouped inside their parent biopolymer chain (Protein, DNA, or RNA) in sequence order
• Pin Favorite Projects and Structures on Welcome Screen: Star recent items on the Welcome Screen to keep favored projects and structures pinned at the top across sessions
• Reset UI to Default Settings: New “Resetting Preferences” section in Preferences → General with a “Reset UI to Default Settings” action to restore window layouts, toolbars, colors, fonts, and presets without altering project files or scientific options
• Disabled Atomic Partial Charges for Coarse-Grained Systems: Disabled atomic partial charge options in Maestro for Coarse-Grained (CG) models where atomic charges are irrelevant
• Decoupled 2D Viewer Settings & Hydrogen Controls: Added a dedicated “2D Settings…” option to the 2D Viewer gear menu (persisted across sessions) independent of global preferences, plus an “Expose All Hydrogens” toggle
• Clarified 2D Structure Preferences Scope: Preferences → 2D Structure explicitly specifies its scope across the Project Table and 2D Overlay, provides a shortcut to Ligand Detection settings, and ensures the 2D Overlay adheres to these preferences

Infrastructure

• Native Apple Silicon Support (macOS ARM64): Replaced x86_64 translation with native ARM64 binaries across the entire suite on macOS, allowing Maestro and integrated backends to execute natively on Apple Silicon without Rosetta 2

Target Validation & Structure Enablement

Protein Preparation

• Easier customization of hydrogen/bond order assignment settings
• Allow interactive termini capping during protein preparation
• Either terminal oxygen can now be rebuilt if missing from input structure

Predictive Tox Panel

• Three new targets have been added including one nuclear hormone receptor (progesterone), one GPCR (CB1), and one protease (MALT1)

Binding Site & Structure Analysis

Desmond Molecular Dynamics

• Added support of nucleotide-based receptors (DNA/RNA) in the Simulation Interaction Diagram (SID)
• New membrane bilayer template for POPE-POPG (3:1)

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

Ligand Preparation

Ligand Preparation and Conformation Generation

• Added ring spear detection to LigPrep to ensure macrocycle conformations with bonds passing through rings are not returned

Empirical and QM-based pKa Prediction

• An improved html report is now available at the end of Macro-pKa calculations

Hit Identification & Virtual Screening

Glide

• Use Generative Glide to screen billions of molecules with generative AI combined with physics-based docking in a fraction of the time of traditional screening to rapidly discover diverse, high-scoring hits

Macrocycles

• Macrocycle Docking script now support docking into cryo-electron microscopy (cryo-EM) density maps
• Macrocycle Docking panel can now be used to dock ligands into cryo-EM density maps with the new map input field
• Output poses for Macrocycle Docking jobs now retain the original input ligand titles

ABFEP

• Efficiently screen structurally diverse chemotypes and novel scaffolds up to 5X faster with high-throughput ABFEP Scan mode
• A representative structure from the solvent leg is now available
• Optionally apply alternative water models

Lead Optimization

Ligand alignment

• Tug Align 2 is now the default macrocycle ligand alignment algorithm in the Maestro Ligand Alignment panel
• The Ligand Alignment panel now exposes advanced alignment options for finer control of alignments of macrocycles

RetroSynth

• Updated RetroSynth reports to include:
• Cover page with high-level overview and vector images
• Faster result generation and smaller file size
• Every solved route, not just the top 30
• Select from custom vendors before launching RetroSynth
• New Stereochemical scoring accounts for variants in stereochemistry in custom stock

FEP+

• A representative structure from the solvent leg is now available
• Added support for nucleotide-based receptors (DNA/RNA)

Protein FEP

• A representative structure from solvent leg is now available
• New interface support to setup and analyze pH-dependent affinity predictions
• FEP+ Residue Scanning now supports protein mutations including non-standard amino acids at scale

Solubility FEP

• A representative structure from the hydration leg is now available

FEP+ Protocol Builder

• Added support for nucleotide-based receptors (DNA/RNA)

Quantum Mechanics

• DFT single point energies and geometry optimizations can be performed within the resolution-of-identity approximation on GPU
• Optical rotation as a function of wavelength is a new property in Jaguar panels

Macrocycles

• Open beta release for Tug Align 2, an improved flexible ligand alignment algorithm for fast alignment of macrocycles and other beyond rule-of-five compounds where standard flexible alignment is unsuitable
• Improved enrichment of native-like macrocycle conformers with Prime-MCS
• Prime Macrocycle Sampling panel default implicit solvent model is now the surface generalized born model
• Improved memory utilization for macrocycle scoring script when running QM scoring jobs

Education Content

• New Tutorial: Exploring Water Wire Effects on Reaction Barriers with AutoTS
• New Tutorial: Affinity Optimization of Macrocycles with FEP+
• New Tutorial: In Silico Multi-parameter Optimization of Protein-Protein Complexes
• New Tutorial: Refining Ligand Poses from Cryo-EM Models to Enable FEP+
• Updated Learning Path: Computational Target Analysis

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Upgrade to Quantum ESPRESSO 7.6
• VASP constraints retained when using POSCAR file as input (command line)
• Support for Broyden optimization in NEB calculations (command line)
• (+MATSCI_QE_SOLVATION) Support for 3D-RISM
• Surface Energy: Option to select slab surface termination groups

Defect Properties

Product: MS DefectPro

• Defect Correction: Support for Freysoldt correction on all OS

Microkinetics

Product: MS Microkinetics

• Multistage workflow for electrocatalysis

Active Learning Optoelectronics

Product: Active Learning Optoelectronics

• Active Learning Optoelectronics: MLFF option for geometry optimization

Reactivity

Product: MS Reactivity

• Reaction Network Viewer: Expanded list of energy-related properties

KMC Charge Mobility

Product: MS Mobility

• Compute KMC Charge Mobility: Improved prediction for zero-field mobility

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Speedup (up to 4 times) with improved algorithms

Advanced Force Field Applications

Product: MS FF Applications

• MLFF Calculation: Output structures returned along the optimization path
• MLFF Fine-Tuning: Support for training with multiple datasets
• MLFF Fine-Tuning: Option to start fine-tuning from a custom MPNICE model
• MLFF Fine-Tuning: Option to customize the fraction of validation set
• MLFF Fine-Tuning: Option to train on data from other MLFF simulations

Transport Calculations via MD simulations

Product: MS Transport

• Ionic Conductivity: Support for solid-state structures as input

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Backmapping: Secondary structure in protein structures retained
• Backmapping: Option to record intermediate structures and trajectories
• Backmapping: Support for antibodies
• Coarse-Grained Sketcher: Support for loading CG structures for editing
• CG FF Builder: NPT ensemble set as default
• CG FF Builder: Improved speed and memory utilization for RDF calculations
• CG FF Builder: Control over the ratio of training from all-atom and CG trajectories
• Coarse-Grained Mapping: Support for mapping from command-line

Materials Informatics

Product: MS Informatics

• Machine Learning Property: 5 new models for properties of inorganic crystals
• MPNICE Embeddings: Option to load results from the file system
• MPNICE Embeddings: Six new machine learning models to select
• MLFF Calculations: Support for parallel simulations
• Solubility ML: Prediction of molecular solubility in non-aqueous solvents

Formulation ML

Product: MS Formulation ML

• Formulation ML Optimization: Returning CSV output
• Formulation ML: Feature Importance reported for individual formulations

Denovo ML

Product: MS Denovo ML

• REINVENT: Access to pre-trained ML models
• Inverse Molecular Design: AI-powered workflow to generate organic molecules with target properties

MS Maestro Builders and Tools

• Agentic Workflow: AI Agent for building Meta Workflows
• Assign Space Group: Option to set up tolerance for symmetry
• Disordered System: Retention of component titles as atom-level properties
• Import Slabs: Additional (49) slab surface models for semiconductor application
• Infrastructure: Visualization of input SMARTS patterns
• Interface Builder: Option to build non-primitive slab surfaces (command line)
• Meta Workflows: (+META_WORKFLOW_QE) Support for Quantum ESPRESSO
• Meta Workflows: Support for Thermal Conductivity
• Partial Concentration: Mixture components labeled after the original entry title
• Periodic Enumeration: Option to set oxidation states for Ewald ranking
• Periodic Enumeration: Option to limit the number of output structures
• Periodic Enumeration: Option to turn off space group assignment for speed-up
• Periodic Enumeration: Option to turn off atom connections for speed-up
• Reaction Path Viewer: Support for MLFF
• Semicrystalline Polymer: UI for assigning head/tail sites on repeat units
• Semicrystalline Polymer: Multiple monomer types in amorphous region
• Semicrystalline Polymer: Improved algorithm for a speed-up of up to 20 times
• Solvate System: Support for MLFF
• Solvate System: Retention of component titles as atom-level properties
• Structured Liquid: Retention of component titles as atom-level properties
• Structured Liquid: Support for MLFF
• Sugar Builder: Option to build with glycosylation patterns

Classical Mechanics

• Droplet: Support for MLFF
• Mixing Enthalpy: (+MATSCI_MIXING_ENERGY) Support for parallel computing on multiple GPUs
• Mixing Enthalpy: (+MATSCI_MIXING_ENERGY) Workflow solution to compute energy of mixing and the Flory-Huggins χ parameter for multi-component polymeric materials
• Polymer Crosslink: Improved structure-scanning algorithm for speed-up
• Umbrella Sampling: Support for job restart/extension
• Script for modifying 3D molecular structure of an RNA (command line)

Quantum Mechanics

• QM Multistage: GPU support for single-point energy and geometry optimization
• QM Multistage: Option to compute optical rotation as a function of wave length
• Adsorption Energy: Support for applying pressure lower than 0.01 atm
• Adsorption Energy: Increased vacuum in PBC for molecules in the gas phase
• Adsorption Energy: Option to include the dipole correction
• Bond and Ligand Dissociation: Option to specify bonds to dissociate
• CREST: Available to run on MS Maestro license
• Optoelectronic Film Properties: Option to compute dipole for all input molecules
• Optoelectronic Film Properties: Giant surface potential (GSP)
• Optoelectronic Film Properties: Spontaneous orientation polarization (SOP)
• Optoelectronic Film Properties: Order parameters for the electric dipole moment
• Optoelectronics: Support for geometry optimization via MLFF
• Phase Diagram: User control over displayed units
• Probe Grid Scan: Support for probing the interior of cage-like molecules

Education Content

• New Tutorial: Designing Workflows with Agentic AI Models
• New Tutorial: Spontaneous Orientation Polarization and Giant Surface Potentials of Thin-Films
• New Tutorial: Microkinetic Modeling of Electrocatalytic Reactions
• New Tutorial: Protein Characterization: Part 3
• New Tutorial: De Novo Design of Novel Compounds with Path Steered Diffusion Model
• New Tutorial: Building Glycans with the Sugar Builder
• New Tutorial: Machine Learning Solubility Prediction
• New Tutorial: Machine Learning Property Prediction for Inorganic Crystals
• Updated Tutorial: Kinetic Monte Carlo (KMC) Charge Mobility

Education Content

Life Science

• New Tutorial: Exploring Water Wire Effects on Reaction Barriers with AutoTS
• New Tutorial: Affinity Optimization of Macrocycles with FEP+
• New Tutorial: In Silico Multi-parameter Optimization of Protein-Protein Complexes
• New Tutorial: Refining Ligand Poses from Cryo-EM Models to Enable FEP+
• Updated Learning Path: Computational Target Analysis

Materials Science

• New Tutorial: Designing Workflows with Agentic AI Models
• New Tutorial: Spontaneous Orientation Polarization and Giant Surface Potentials of Thin-Films
• New Tutorial: Microkinetic Modeling of Electrocatalytic Reactions
• New Tutorial: Protein Characterization: Part 3
• New Tutorial: De Novo Design of Novel Compounds with Path Steered Diffusion Model
• New Tutorial: Building Glycans with the Sugar Builder
• New Tutorial: Machine Learning Solubility Prediction
• New Tutorial: Machine Learning Property Prediction for Inorganic Crystals
• Updated Tutorial: Kinetic Monte Carlo (KMC) Charge Mobility

LiveDesign

What’s Upcoming in 2026-4

• Access Lilly TuneLab in LiveDesign to advance preclinical drug discovery with proprietary Lilly AI models
• Any user can now import a biologic entity through a file upload. The original registrar can overwrite the entity’s metadata, and any user can append metadata
• Import published assay data through file uploads for small molecules. Use SDF, CSV, MAE, or .xlsx to make the assay data accessible across all LiveReports
• Analyze SAR with the SAR Analysis Dashboard
• See LiveDesign server load through the System Health Tool
• Combine Filter elements into Groups