Release Notes

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• 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

Force Field

• New OPLS5 Force Field (beta): Significant improvement in the accuracy of cation-pi and ionic group interactions via the addition of limited polarizability in relative binding-FEP+ and Desmond. Available as a new option alongside the default OPLS4

Workflows & Pipelining [KNIME Extensions]

• 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

KMC Charge Mobility

Product: MS Mobility

• Compute KMC Charge Mobility: Charge transfer computed based on center-of-mass distances

Materials Informatics  

Product: MS Informatics

• Formulation ML: Support for input data with missing component names / SMILES
• Formulation ML: Support for Set2Set and graph-based models and descriptors added
• Formulation ML: Option to remove highly-correlated descriptors (command line)
• Formulation ML: Option to control the training set size
• Formulation ML: Support for classification mode
• Formulation ML: Feature-importance analysis based on Shapley additive explanations (SHAP)
• Machine Learning Property: Improvements in prediction models available for download
• Machine Learning Property: Prediction of oxidation and reduction potentials
• MD Descriptors: Support for formulations-focused descriptors

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Coarse-Grained Force Field Builder: Automatically map atomistic systems to Martini particles (command line)
• Coarse-Grained Force Field Builder: Fit Martini parameters (command line)

Reactivity

Product: MS Reactivity

• Nanoreactor: Improved default settings
• Nanoreactor: Speed-up of xTB frequency calculations
• Nanoreactor: Improved deduplication algorithm for products
• Nanoreactor: Improved parallelization algorithm
• Nanoreactor: Option to remove high-energy products
• Nanoreactor: xTB free energy used to rank-order products
• Auto Reaction Workflow: Prevention of excessive equilibrium constant calculations from permutations

Microkinetics

Product: MS Microkinetics

• Microkinetic Modeling: Support for the use of analytical Jacobian
• Microkinetic Modeling: Option to specify collision factor
• Microkinetic Modeling: Results returned for cases that did not reach a steady state
• Microkinetic Modeling: Option to list chemical equations from the input reaction network

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Reaction-template based solution for dynamic simulations of materials systems near battery electrodes

MS Maestro Builders and Tools

• Density Profile: Visualization of density isosurfaces
• Complex Builders: Option to clean up geometry using xTB
• Semicrystalline Polymer: Support for polyvinyl alcohol (PVA)
• Solvate System: Protocol to manage output with more than 2M atoms
• Structured Liquid: Protocol to manage output with more than 2M atoms
• Structured Liquid: Improved and expanded built-in lipid library

Classical Mechanics

• Thermal Conductivity: Solution to predict thermal conductivity of solids

Quantum Mechanics

• Adsorption Enumeration: Improved algorithm to define surface atoms
• Adsorption Enumeration: Heavy-atom filter for reactive atoms
• Amorphous NMR: Isosurface data available from QM calculations

Education Content

Life Science

• New Tutorial: Ligand Binding Pose Prediction for FEP+ using Core-Constrained Docking (NEW)
• New Tutorial: Ligand-Based Virtual Screening Using Phase (large-scale rework from the ground up)

Materials Science

• New Tutorial: NMR Spectra Prediction
• New Tutorial: Thermal Conductivity
• New Tutorial: Solid Electrolyte Interphase Calculations
• New Tutorial: Building a Semicrystalline Polymer
• Updated Tutorial: Machine Learning for Formulations
• Updated Tutorial: Update tutorials for switch to RDKit (affects multiple tutorials)

LiveDesign

What’s New in 2024-2

• Biologics Support
  • Upload peptides, monoclonal antibodies, bispecific antibodies, Fab, Fab2, Fv, DNA, and RNA
  • Biologics automatically get broken down into their component chains and can be visualized in composite rows
  • View and align sequences in a sequence viewer
  • Upload experimental data and metadata
  • View 3D model results and apply styling
  • View an antibody’s hierarchy in 3D visualizer and select and style at the full biologic, domain (ex: VH, CH1), subdomain (ex: HCDR3), or residue level
  • Full support within Models, MPOs, Formulas, Freeform columns, Forms, Tile View, Filters, and Search
  • Search and Filter for Biologics based on the properties of their chains
• Updated User Management in the Admin Panel
  • See and update all Users’ ACL and details on single page
  • Quickly add and remove multiple users at once
  • Bulk update users’ roles, projects, and license status
  • Create a project and add users, groups, admins to the project on single page
  • Project and Group details pages give clearer statistics on users and access control flow
  • Choose to send or resend a welcome email on updates
  • Sync users between LiveDesign and externally hosted, read-only LDAP, to pre-populate users before their first login
• One-click to view 3D model results in Maestro: Click a link in a 3D model cell to automatically open Maestro and view the result. Note that this only works in Windows, using Maestro version 24-2; Mac and Linux support are forthcoming in Maestro’s 24-3 release
• Structure Groupings for the 3D Visualizer
  • Group any number of 3D outputs in a single structure group, beyond the historic Ligand + Protein combination
  • Add custom group titles to change the displayed column title
  • View multiple ligand poses or protein poses in the 3D visualizer content panel
• Control Display styles in Ligand Designer
  • Style selected atoms, resides, and chains from a new toolbar within the 3D canvas in Ligand Designer
  • Apply custom styling to Proteins and Ligands within a Ligand Designer session
  • Use 3D tools within Ligand Designer, such as export, zoom, and screenshot
• Complex Filters: Combine filter conditions using AND or OR logical operators
• Published Limited Assay Columns: Publish limited assay columns so they appear in the Data & Columns tree, and are available for use in published column-as-parameter models, MPOs, and published formulas
• Pinned Rows: Click a button on a row or a Tile to “pin” the compound to the top of the LiveReport
• UX Improvements
  • Forms
    • Toggle the number of tiles to show in each row in a Kanban widget
    • Freeform column cells now render larger editing areas in the Matrix Widget when the cells are small
  • Plots
    • Plot can’t be created or edited in read only LRs
    • Delete plots directly from the visualize panel, without opening them first
    • Search for columns in plot axis selection dropdowns
  • Spreadsheet interactions
    • Freeze multiple columns at once via the column menu
    • Double-click on a Freeform column cell to edit its value
    • The Run button for click-to-run models is now displayed as a solid color
    • Right-click on a LiveReport tab to reveal the LiveReport menu
  • 3D Visualizer
    • Downloaded files from the 3D visualizer now show the same labels in Desktop PyMOL instead of hashed values
    • Binding Site Interaction Map is turned off by default when opening a Ligand Designer session
  • Miscellaneous 
    • The login page now allows submitting either Single sign-on or username + password credentials
    • Export the Tile View configuration to PPTX using LDClient
    • Archive a model without fixing errors in the model settings
    • The Job Manager gadget table now resizes as the tool is resized
    • Click Help icons in the Create Freeform Column dialog, Create Formula column dialog, and the Define New Multi-Parameter Optimization dialogs to navigate directly to the user manual
    • Click an icon within the Data & Columns Tree LiveReport tab to scroll to the column in the LiveReport
    • Drag and add multiple scaffolds to the R-group enumeration scaffold sketcher
  • TaskEngine workers now scale up when the number of submitted jobs increases
  • The Schrodinger Suite python method “from schrodinger.structure import SDReader” has been deprecated, and scripts should instead call “from schrodinger.structure import StructureReader”

What’s Been Fixed

• The Landing Page Overview would occasionally fail to show the most recently added compounds, and now correctly shows them
• Columns that are added to LiveDesign via the Data Integrator are now set to the correct datatype
• LiveReports no longer show duplicate rows for a Real and a Virtual after uploading experimental data via ACAS
• LiveDesign now correctly opens the most recently opened Project and LiveReport after logging in
• Users can now log out of LiveDesign when Single Sign-On is enabled
• Freeform column picklist options order would previously change, and is now maintained according to the configuration set within the Edit Freeform Column dialog
• Security
  • CVE-2023-44487 has been patched
• Admin Panel
  • Uploading a file in the Admin Panel now works correctly when the filename is identical to the file that is being replaced
  • The Last Modified Date shown in the Admin Panel’s Protocol page and Protocol List page now correctly updates for all changes to the Protocol
  • The “Last Login” date field within the Admin Panel’s User page now correctly updates
• File Exports
  • Enhanced stereo labels now show in all images in PowerPoint exports
  • Exporting Tile View to PowerPoint now correctly warns the user when attempting to show more than 8 compounds per slide
• Forms
  • Tiles now render correctly in Tile View widgets, when the Tile View widget is in the same container as another widget
  • Tooltips in Tile View would previously get frozen after displaying R-group decomposition results, and how correctly show data for each cell
  • Tile view tooltips now render correctly-sized R-groups when hovering over a R-group decomposition cell
  • The Forms Entity Image widget now correctly shows the ID of the entity
  • Forms drilldown from a row-per-compound widget to a row-per-pose widget now correctly shows the poses only for the selected compound(s)
  • The Forms Matrix widget now shows the entity image for Generic Entities
• LDClient
  • A ‘parent_row_key’ has been added to the LDClient RowInfo object within LiveReportResultsMetadata, which identifies which rows are child composite rows in the LiveReport
  • LDClient ldclient.LDClient.refresh_db_constants method and the AboutInfo remaining_read_only_licenses_count field have been deprecated and removed
  • LDClient now correctly returns a LiveReport’s filters, when the filters include a substructure query
  • LDClient’s ModelTemplateVarType enum now includes LIST_INPUT and RDKIT_MOL
  • Scripts calling LDClient occasionally needed to execute a LiveReport, and include a manually programmed sleep to get results. LDClient now includes a method mutate_then_wait, which allows code to wait on actions to be completed before continuing (such as adding rows to a LiveReport)
• Ligand Designer
  • Ligand name shows up correctly in Ligand Designer, when the LiveReport is in row-per-pose mode
  • Grid files can now be changed for existing Ligand Designer configurations in the Admin Panel
• Maestro Export
  • LiveReport exports from LiveDesign to Maestro now work correctly when two Real compounds are linked to the same Virtual compound
  • Maestro exports to LiveDesign with published data are now faster
• Matched Molecular Pairs
  • Previously calculated Matched Molecular Pair analyses have been deleted due to a backwards-incompatible Python library upgrade, and must be re-run
  • The Matched Molecular Pairs tool now shows an error message when large LiveReports fail to complete the matched pairs computation
• Spreadsheet Interactions
  • Searching by substructure in the active LiveReport will now deselect existing row selections, and select the matching substructures
  • Compound orientations in the sketcher are now saved when adding the compound to a LiveReport, using a scaffold in R-group decompositions, using a scaffold for compound alignment, and using compounds in enumeration
  • The row-per-model toggle is no longer obscured when the visualizer panel is open
  • Searching a LiveReport via the magnifying glass now correctly navigates to the first matching string
  • Calculated properties that appear below the sketcher now truncate long column names to avoid an overlap with the calculated value
  • Attempting to recalculate an archived model would show flashing cells, as if the calculation has been started (despite no calculating being started), and will now show an error message
  • Searching for metadata within assay columns’ Edit Tooltip Content now correctly filters content that does not match the query
  • Copy and Paste coloring rules for R-group decomposition columns
  • Copying a compound into the sketcher via the row menu’s “Use in → Design/Search Sketcher” option will now correctly overwrite any compound within the sketcher
  • Importing a compound multiple times to the sketcher using its ID will now correctly show the compound’s structure
• Plots
  • Box plots now show a border around selected outlier data points to make them more noticable
  • Scatter plot tooltips now show assay datapoint operators, such as ‘greater than’ and ‘less than’