Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• New Welcome Screen on startup provides quick access to common tasks such as creating and opening projects and importing structures
• Modernized and streamlined Project Table for enhanced usability
  • New Table Configuration pane allows fast switching between Light and Dark themes and toggles visibility of the ePlayer and Property Tree.
  • New Gadgets Menu provides convenient access to Charts and the 2D Viewer
• New Workflow Action Menu (WAM) to view spectroscopy results from Jaguar and Jaguar Spectroscopy calculations in the Project Table

Target Validation & Structure Enablement

Protein Preparation

• Improved minimization protocol to support broader coverage of biological and chemical systems
• Produce more reliable prepared structures by expanded coverage of equivalent tautomeric ligand states
• More easily view serious structural issues by filtering diagnostic reports with a severity threshold
• New ‘Missing Atom’ tab on the Diagnostics panel enables select sidechain and loop modeling

Cryo-EM Model Refinement

• GlideEM poses are now sorted by GlideScore which is more discriminating in ranking low RMSD structures than Denscore

Ligand Preparation

Ligand Docking

• Faster Glide scoring and docking with optimized Glide (Beta): Screen larger libraries and find better candidates with optimized Glide, including enhanced Active Learning Glide and Python API support
  • Same industry-leading Glide docking funnel and scoring functions, Emodel and GlideScore
  • Faster turnaround with same compute resources for Active Learning Glide and AutoDesigner
  • Advanced Python API support offers easy automation and file control over docking process for greater experimentation
  • Accessible through the new Ligand Docking panel that enables setup of Active Learning and Glide calculations

ABFEP

• Energy Decomposition data is now reported in Analysis PDF reports

Lead Optimization

FEP+

• New FEP+ Pose Builder workflow for automatically generating high-quality ligand alignments (Beta): Generate FEP-ready poses faster and run FEP+ at scale with an automated workflow designed for unbiased selection and robust atom-mapping
• Ability to read and write FEP+ Protocol files directly in the FEP+ Panel
• Improved Classification matrix styling
• Kendall’s tau statistic added to the statistical metrics reported
• Improvements to exported FEP+ data in csv/xls formats
• Added ‘None’ as a new Hot Atom Rule

Protein FEP

• FEP+ Residue Scan supported in Protein FEP+ for Ligand Selectivity panel

Constant pH Simulations

• Added support for Cysteine residues

FEP+ Protocol Builder

• Sharply reduced compute resources to run default workflow by shrinking initial simulation times to 0.5 ns and extended times to 10 ns
• Seamless interconnection as FEP+ Panel can now Read/Write Protocol Builder files
• Bias the selection of protocols to extend including compute efficiency via Pareto analysis (command line only)
• Added support for covalently bound ligands
• Ability to optionally sample charge states of GLU, ASP, LYS, ARG, and CYS in protocol optimization

De Novo Design

AutoDesigner – R-group Design

• New R-group Similarity score feature to focus ideation around compounds of interest
• New Design Rationale capability to improve ADME endpoints with respect to reference ligands

Alternative Modalities

Bifunctional Degraders

• Expanded support for protein degrader modeling with the new Degrader Sampling Workflow (Beta): Generate accurate degrader ternary complexes through integration of protein-protein docking and linker sampling in a structure-based workflow

Biologics Drug Discovery

• Augmented AI/ML capabilities for biologics with machine learning-based T-Cell Receptor (TCR) structure prediction (Beta): Perform high throughput structure prediction and large scale modeling of TCRs with the ImmuneBuilder deep learning model and Prime
• New Macromolecular Pose Filtering panel to filter native or near native poses from an ensemble of complexes using experimental data such as HDX-MS

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• A new environment variable for the location of Quantum ESPRESSO binary

Transport Calculations via MD simulations

Product: MS Transport

• Thin Plane Shear: Selection of slab region by molecular units

KMC Charge Mobility

Product: MS Mobility

• Compute KMC Charge Mobility: Predictions based on Schrödinger’s new mobility engine

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Updates to existing models
• Machine Learning Property: Prediction of triplet reorganization energy
• Machine Learning Property: Prediction of S1-to-T1 energy gap (∆EST)
• Machine Learning Property: Predictions from the interactive mode automatically added to the Project Table
• MLFF Calculations (Beta): Single-point energy and geometry optimization tool using Schrödinger’s latest machine-learned force fields

Formulation ML

Product: MS Formulation ML

• Formulation ML: Support for custom ingredient descriptors
• Formulation ML: Support for creating models using multiple CPUs in parallel
• Formulation ML: Support for setting mixtures as individual components
• Formulation ML Optimization: Workflow solution to optimize materials formulations

Layered Device ML

Product: MS Layered Device ML

• OLED Device ML: Workflow solution to predict OLED device performance
• Optoelectronic Device Designer: Use ML OLED device models to predict performance

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Automated CG Mapping: (+AUTOMAPPING_MARTINI_PROTEIN) Support for proteins in automated mapping and parameterization for Martini
• Automated CG Mapping: Accurate mapping for carbohydrate systems
• Improved threshold for momentum errors in CGMD simulations
• CG FF Builder: Parameters for water-water interactions fixed by default

Dielectric properties

Product: MS Dielectric

• Complex Permittivity: Option to run replicates in parallel

Reactivity

Product: MS Reactivity

• Reaction Network category created under the Materials task menu
• Reaction Workflow renamed to Reaction Network Profiler
• Auto Reaction Workflow renamed to Reaction Network Enumeration Profiler
• Reaction Network Profiler: Option to run conformational search using CREST
• Reaction Network Profiler: Conformational search included in restarts (command line)
• Nanoreactor: Option to screen products by energy relative to reactant state
• Nanoreactor: (+ELEMENTARY_REACTION_NETWORK) Support for the Elementary Reaction Network workflow

Microkinetics

Product: MS Microkinetics

• Microkinetics Deposition Analysis: Workflow solution to run post-analysis of microkinetic simulations in deposition or etch processes of solid materials
• Microkinetic Modeling: (+MATSCI_MKM_INTERACTIONS) Support for simple quadratic adsorbate-adsorbate interactions

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Option to block intramolecular reactions (command line)
• Solid Electrolyte Interphase: Option to use DFT charges for new species

Crystal Structure Prediction

Product: Crystal Structure Prediction

• Crystal Structure Prediction: Interface and workflow to predict crystal structures and polymorphs for a given molecular compound

MS Surface

Product: MS SurfChem

• Adsorption Enumeration: Access to workflow assessing reactive adsorption
• Desorption Enumeration: Workflow solution for assessing desorption of multiple molecules

MS Maestro User Interface

• Direct link from the task menus to Materials Science Panel Explorer page

MS Maestro Builders and Tools

• Structured Liquid: Automatic standardization of custom lipids
• Polymer: Improved dihedral setups for multiple shortest-length backbones
• Organometallic Conformational Search: Option to run conformational search using CREST

Classical Mechanics

• Evaporation: Option to export the results as CSV file
• MD Multistage: Center of mass motion removed for coarse-grained systems
• Thermophysical Properties: Option to save trajectory energy file
• Umbrella Sampling (Beta): Workflow solution for umbrella sampling of membranes

Quantum Mechanics

• Adsorption Energy: Support for reactive adsorption and desorption energies
• Adsorption Energy: Improved assessment of entropy loss during the adsorption
• Bond and Ligand Dissociation: Option to set product charges from formal atomic charges
• Bond and Ligand Dissociation: Support for PCM and SMD solvent models
• Bond and Ligand Dissociation: Improved 2D visualization of charges and radicals in product fragments
• Crest: UI for semiempirical QM based conformational search using CREST
• Optoelectronic Film Properties: Support for multiple reorganization energies as input for computing intersystem crossing (ISC) rate
• Optoelectronic Film Properties Viewer: Support for user-input reorganization energies to instantly re-evaluate SEET rate
• Thermochemistry Viewer: Support for viewing reactive adsorption and desorption energies
• Trajectory Density Analysis: Improved naming scheme for atom groups

Education Content

Life Science

• New tutorial: Exploring Protein Binding Sites with Mixed-Solvent Molecular Dynamics
• New tutorial: Introduction to T-Cell Receptor Modeling with BioLuminate
• Updated tutorial: Antibody Visualization and Modeling in BioLuminate
• Updated tutorial: Peptide Modeling with BioLuminate
• Updated tutorial: Target Analysis with SiteMap and WaterMap
• New QRS: Structure Reliability Report
• New QRS: Custom Reactions for Covalent Docking
• New QRS: Mixed-Solvent Molecular Dynamics
• Updated QRS: GlideWS Model Generation
• Updated QRS: MM-GBSA Residue Scanning

Materials Science

• New Tutorial: Umbrella Sampling
• New Tutorial: Crystal Structure Prediction
• New Tutorial: Optimization of Formulations Using Machine Learning
• New Tutorial: Machine Learning for OLED Device Design
• New Tutorial: Nanoemulsions with Automated DPD Parameterization
• New Tutorial: Applied Machine Learning for Formulations
• Updated Tutorial: Atomic Layer Deposition
• Updated Tutorial: Design of Asymmetric Catalysts with Reaction Network Enumeration Profiler (previously AutoRXNWF)
• Updated Tutorial: Machine Learning Property Prediction
• New QRS: CREST
• New QRS: Microkinetics Deposition Analysis

LiveDesign

What’s New in 2025-2

• Import Antibody-Drug Conjugates from SimpleSchema
• Freeform Columns
  • New “Comment” type: Write threaded conversations within a Freeform column, and track usernames and timestamps
  • Creating a Freeform column is now performed using a wizard that permits selecting the data type of the Freeform column first, and then specifying the Freeform column details
• Formulas
  • Formulas support multiple values: Input cells to formulas can now contain multiple valuesFormulas can output multiple values, aligned by Experiment, Lot, or Pose. New formula functions were created to handle input cells with multiple values: cellAggregation(), join(), any(), and all()
  • Failed model cells can now be used as formula input
  • A new isFailed() function returns true for any failed model cells, and false otherwise
• Dashboards (Previously called Landing Pages)
  • Biologics and Generic entities are now supported on Landing Pages
  • Project Admins can edit the project description directly on Landing pages instead of configuring it from the Admin panel
  • Project admins can now select a date range via the ‘Time range’ filter in Landing Page Entities Section to look for entities added within a range of days
  • A ‘Bookmark LiveReport…’ option has been added in the LR grid menu and clicking on the option redirects the user directly to the new Bookmark page (in Landing pages) in a new window. The LiveReport’s name gets auto-populated in the LiveReport info section of the window
• Admin Panel: Add multiple new users at once with a CSV upload
• Sequence Viewer
  • Perform sequence-activity relationship analyses by viewing multiple data columns in the sequence viewer
  • Select a reference sequence even when there’s no alignment
  • Retry failed alignments and cancel running alignments
• Unification of Generic Entity and Biologics Import Pipeline: Generic Entity and Biologics import tabs are collapsed into “Biologics/Others” tab. All entities imported from “Biologics/Others” tab are virtual entities. Allows csv import of metadata on virtual entities.
• UX Improvements
  • R-group Decomposition highlighting can now highlight the bond lines, rather than showing a halo-style highlighting around the bond
  • Users now have the quick filter options to filter by any/all types of Entities on Advanced search, just like in the Filter panel. They can choose from the options of All, Compound, R-group, Biologic and GE
  • Users can now drag a compound structure to Advanced search to create a new substructure query, like in Filter panel
  • Export data qualifiers (e.g., the greater than symbol ‘>’) as a separate column in data exports
  • Exporting a LiveReport: Choose whether to include filtered out rows, or exclude them, when exporting via the User Interface or LDClient
• Structure Processor: A new “STRICT” processor setting allows compounds with valence violations and other invalid chemistries to be accepted or rejected by the processor. By default, compounds with valence violations are not permitted

What’s Been Fixed

• Data and Columns Tree
  • Attempting to favorite published Limited Assay Columns in the Data & Columns Tree would fail, and now those columns can be favorited
• Filters
  • LiveReport filters in Complex view would show additional brackets to the filter conditions, and the filter conditions would rearrange, when columns were removed from LiveReports. The arrangement of filter conditions are now properly retained and brackets do not appear
  • Removing a column from a LiveReport while viewing the Filter panel would change the Filters view from simple mode to complex mode, and now keep the view in simple mode
  • Filtering out a frozen row would show flashing squares in the first row in the main spreadsheet, and now correctly shows that row’s data
• Forms
  • Copying text from a Forms widget previously showed dotted lines in multiple widgets, and incorrectly indicated that text from multiple widgets was copied. Dotted lines now appear only around the cells within a single widget that were most recently selected
  • Forms annotation widgets would not persist styling changes (e.g., font color), and now correctly persist the changes
  • Matrix widgets included excess whitespace around values; the minimum row height has been reduced to eliminate excess whitespace
  • Viewer users could not see 3D results in the 3D Visualizer nor in Forms, and now can view 3D results
• LiveReport Management
  • LiveReport tabs would disappear after logging out and logging in, and now correctly appear after logging back in
  • Clicking a LiveDesign hyperlink would fail to open the linked LiveReport, and instead would open the user’s last-opened LiveReport; clicking hyperlinks now correctly opens the linked LiveReport
  • The Create New LiveReport dialog now permits filtering the list of LiveReport templates
  • Attempting to apply a template to a LiveReport that contained filters would fail, and now applying a template succeeds
  • Overwriting a template would create a new template, instead of overwriting, and now correctly overwrites the template
  • Applying a template to a LiveReport would not include Limited Assay Columns contained within the template, and now correctly include Limited Assay Columns
  • Duplicating a LiveReport would not include all columns by default, and now includes all columns by default
• Maestro Upload
  • Importing structures into Maestro from LiveDesign would occasionally fail when task status of “FINISHED” was reported before the result URL was available, and now correctly imports structures
  • Importing structures into Maestro from LiveDesign would fail if a LiveDesign model returned an empty protein file, and now the empty protein file will be skipped and not imported into Maestro
• Model Creation
  • Configuring a Protocol in the Admin Panel to use a ${RDKIT-MOL} macro would prevent the creation of a parameterized model in the LiveDesign UI, and now correctly allows creating a parameterized model
• Plots
  • Plot tooltips could not be dragged and moved after pinning to the screen, and now can be dragged to a new position after pinning
• R-group Decomposition
  • Reordering R-group Decomposition scaffolds would eliminate coloring rules and sorting rules for R-group columns, and now correctly maintains coloring rules and sorting rules
• Search
  • Advanced Search would occasionally return extra entities that didn’t match the search conditions on columns, when those columns had an undetermined data type, and now does not return extra entities
• Sequence Viewer
  • Horizontally scrolling the sequence viewer would reset the ruler, and show the wrong residue numbers at the top, and now shows the correct residue numbers
• User Administration
  • User email addresses would not save in LiveDesign when using Single Sign-on, and LiveReport notifications would not be emailed to users. Email addresses and are now correctly saved
  • Welcome emails for new users would include an incorrect LiveDesign URL, and now include the correct URL