Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• 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

Workflows & Pipelining [KNIME Extensions]

In LiveDesign:

• 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

Binding Site & Structure Analysis

SiteMap

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

Desmond Molecular Dynamics

• 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

Mixed Solvent MD (MxMD)

• Improved organization of output structures and data in prjzip file

Hit Identification & Virtual Screening

• 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)

Ligand Preparation

Hit Analysis

• Filter chemotypes by SMARTS in Hit Analyzer Panel

FEP+

• 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

Protein FEP

• 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

Solubility FEP

• Expanded OPLS5 support for Solubility FEP simulations

FEP Protocol Builder

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

Biologics Drug Discovery

• 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

Materials Science

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

Transport Calculations via MD simulations

Product: MS Transport

• Diffusion: Support for non-orthorhombic systems as input

Materials Informatics  

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 (CG) Molecular Dynamics

Product: MS CG

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

Reactivity

Product: MS Reactivity

• 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

Microkinetics

Product: MS Microkinetics

• 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

MS Maestro Builders and Tools

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

Classical Mechanics

• 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

Quantum Mechanics

• 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

Education Content

Life Science

• 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

Materials Science

• 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

LiveDesign

What’s new in 2024-3

• Uploads from Maestro to LiveDesign could fail if the LiveDesign project had more than 32,000 columns, and now complete successfully regardless of the number of columns
• LiveReports that contained columns with many values would show red error bars at the top of the LiveReport, and now no longer show the red error bars
• LiveReport tabs would disappear after logging out and logging in, and now correctly appear after logging back in
• New LiveDesign Learning module for rapid AI/ML molecular property predictions: Enables highly scalable, automated AI/ML pipelines for drug design
  • *LiveDesign Learning is now called LiveDesign ML
• Accelerated scaffold and R-group design with AutoDesigner Core Design: Automatically generate and optimize novel cores and R-group(s) simultaneously
• Delete Published Freeform column and Formula columns from the Data & Columns Tree
• Biologics:
  • Sequence-activity relationships in the Sequence Viewer:
    • Ability to add a quantitative column from the LR in the viewer
    • Correlate the changes in the residues and the activity data with the heatmap
  • There would only be one option when trying to import the Biologics data via csv and the option “Import As Single Entity for CSV” won’t show now.
  • Performance of structure hierarchy loading and item selection through hierarchy panel in the 3D Visualizer are improved.
  • Double-clicking an item in the hierarchy zooms to that selection in the 3D Visualizer workspace.
  • Set gap penalties in the sequence viewer to generate more useful alignments
• Landing Pages:
  • The Landing page now links to a specific URL and enable bookmarking the Landing Page in a browser
  • Download resources and files from the Landing Page Resource page
• Spreadsheet View:
  • A warning message alerting the user to expect decreased performance now appears on LiveReports that contain more than one million cells
  • Entity images no longer enlarge when hovering over the image, and can now be zoomed by clicking a magnifying glass button that appears to the right of the entity image
• The User details page in the Admin Panel now shows a warning that unlicensed usernames will not appear in dropdown lists throughout LiveDesign
• Models now support date and datetime returns
• Forms Matrix Widget now render larger editing areas for Freeform column cells when the cells are small

What’s Been Fixed

• LiveReports would show red error bars when multiple input values to a parameterized model changed simultaneously in the spreadsheet, and now the LiveReport loads correctly
• Popping out a model column’s cell that contained and image would open two tabs in the browser (one tab with the image, and one blank tab), and now only opens a tab with the image
• LiveReports would occasionally lose their filters, and the filter panel would appear blank, but no longer lose their filters
• Changing a user’s role within a Single Sign-on Identity Provider would not update the user’s role within LiveDesign when they logged out and logged back in, and now the role changes are correctly used after the user logs out of LiveDesign and logs back in
• Changes to parameterized model in the Admin Panel (e.g., the Title or Folder) would not save after clicking the Save button, and now correctly save and update the parameterized model
• Changes to a “set fixed” protocol parameter get passed along to the dependent model or parameterized model without breaking them.
• The Formula Substructure Search function incorrectly reported the count of substructure matches as 1, even if there were multiple matches, and now correctly reports the total number of substructure matches
• Adding a new project with an identical name to an archived project provided a cryptic error message, and now provides a clear message instructing the user to choose a different name
• When many LiveReports were open, the active LiveReport tab would disappear when left-side panels were opened, and now the active LiveRepot tab remains visible
• Newly created models would not inherit the Recalculate Model option defined in the protocol, and would default to the “Automatically” option, and now the models correctly inherit the option defined in the protocol
• Parameterized models that have had their columns renamed in the Admin Panel would show the old, original column names when that model was added to LiveReports, and now correctly show the updated column name
• The user interfaces of the Filters panel and Advanced Search panel have been unified
• Changing the column widths within the LiveReport picker caused the column header to misalign with the column contents, and now the header remains aligned
• The prefix (Global) would appear repeatedly for templates in the Global project that were updated and overwritten, and now templates in the Global project only show a single (Global) prefix after they are updated and overwritten
• Maestro would not import 3D results from LiveDesign when the 3D column title was renamed, and now correctly imports all 3D data regardless of the column title
• LiveDesign would occasionally freeze due to a database lock, and now no longer will freeze
• Opening a model attachment from the main spreadsheet (e.g., a LID from a Glide model) would fail to show the image, and now correctly shows the image
• 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
• The Project Picker would appear after a five-second delay when there are a large number of projects to show, and now the Project Picker appears instantly
• The sequence viewer would occasionally show incorrect colors and tooltips for non-natural amino acids, and now shows the correct information
• Hovering over a residue in the sequence viewer would cause the viewer to scroll to the top, and now the scroll position remains does not change
• Plot tooltips could not be dragged and moved after pinning to the screen, and now can be dragged to a new position after pinning
• Model results would occasionally appear as Failed in the LiveReport, when in fact the model ran successfully, and now model results correctly show results in the LiveReport