Release Notes

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Added support for interactive nonstandard protein residue mutation via the Workspace context menu [2023-2]
• Save up to 5K resolution GIFs (Workspace -> Animate) [2023-2]
• Reduce unexpected visual clutter with new preference to limit the number of atom labels [2023-2]
• Maestro to PyMOL connection [2023-2]
  • Create a simple PyMOL movie from Maestro scenes
• Maestro to LiveDesign connection [2023-2]
  • Connect to LiveDesign servers with new access point and connection status indicator
  • Retain and reuse single sign on (SSO) tokens to streamline the login process
  • Benefit from a streamlined process of pushing Maestro data into LiveDesign via the Export panel
• Export Structures – New option to export MD-ready structure / trajectory to CMS file [2023-2]
• New “Show Atom Properties (beta)” panel [2023-2]
  • List multiple atom properties for selected atoms
  • Display SMARTS/SMILES patterns for contiguous selected atoms, including the SMARTS index of the hovered-over atom

Workflows & Pipelining [KNIME Extensions]

• Includes the latest version of KNIME [2023-2]
• Improved usability of the Extract Properties node configuration panel [2023-2]
• Updated LiveDesign nodes and protocols: [2023-2]
  • Adaptable input column checking of the LiveDesign input node
  • KNIME protocol section to install extra KNIME extensions is more robust

Target Validation & Structure Enablement

Protein Preparation

• Bond orders and charges can now either be re-assigned or only added to ligands and residues with missing bond orders [2023-2]

Protein X-Ray Refinement

• Improved robustness when running Phenix/OPLS [2023-2]
• New plots to inspect the best refinement statistics from Phenix/OPLS weight scans [2023-2]
• Phenix/OPLS weight scan automatically choses a near-optimal combination of refinement parameters [2023-2]

AlphaFold Download / Process

• Downloaded AlphaFold structures are returned with an automatically created heatmap of the PAE matrix [2023-2]
• Processed AlphaFold structures can now be optionally capped and the pLDDT threshold changed [2023-2]

Multiple Sequence Viewer/Editor

• New ability for the detection and annotation of Vernier zone residues in antibodies [2023-2]

IFD-MD

• Added visual indicator when the target ligand is missing torsional parameters [2023-2]

Desmond Molecular Dynamics

Improved plotting for Trajectory Plots [2023-2]

Hit Identification & Virtual Screening

Ligand Preparation and Conformation Generation

• Full support for Epik 7 pKa predictions within the LigPrep interface and command line invocation [2023-2]

Empirical and QM-based pKa Prediction

• Conjugate acid/base labels are now included in the Epik 7 log file [2023-2]

Hit Analysis

• Release of the new Hit Analysis interface to streamline interactive analysis and selection of hits from virtual screening campaigns based on molecular properties, ligand feature locations, and shape alignments [2023-2]

Active Learning Applications

• Added ability to train on preexisting FEP data for relative and absolute AL-FEP [2023-2]
• Added histogram of compounds prioritized by machine learning for relative and absolute AL-FEP [2023-2]
• Modified default machine learning settings to improve out-of-the-box performance of relative and absolute AL-FEP [2023-2]

ABFEP

• New capability for fast filtering of inactive ligands to dramatically improve ABFEP throughput [2023-2]

Lead Optimization

Macrocycles

• Improved atom mapping in FEP+ maps for macrocycles [2023-2]

FEP+

• New functionallity to auto-populate state populations in the FEP+ interface [2023-2]
• Improved reporting of results in a single column (val ± err) in the overview tab of the FEP+ interface [2023-2]
• Option to automatically merge force field parameters generated during an FEP+ job with those defined in your Maestro preferences [2023-2]
• Option to select alternative water models for Relative Binding FEP+ via Advanced settings [2023-2]
• Fast filtering of inactive ligands to dramatically improve ABFEP throughput [2023-2]
• Improved atom mapping in FEP+ maps for macrocycles [2023-2]

Protein FEP

• Ability to simultaneously predict protein thermostability with every protein/ligand selectivity simulation [2023-2]
• Option to interactively edit perturbation topologies for protein residue mutations in FEP+ interface [2023-2]

Constant pH Simulations (Beta)

• Greatly improved accuracy in protein pKa predictions through improved sampling of the physical end states of titratable residue side chains in FEP+ [2023-2]

Quantum Mechanics

• New ability to plot excited state energies in rigid and relaxed coordinate scans [2023-2]
• Support for alignment based on uniform scaling in the VCD/IR spectrum_align utility [2023-2]

Semi-Empirical Quantum Mechanics

• Capability to use GFN2-xTB from within Jaguar and in Jaguar-based workflows [2023-2]

Biologics Drug Discovery

• Improved protein descriptor calculation throughput with ability to run in parallel over multiple CPUs [2023-2]
• Up to 5x speedup in protein surface calculations [2023-2]
• Modeling of single-chain Fvs is now incorporated into the antibody structure-prediction interface [2023-2]
• Modeling of F(ab)2 formats is now integrated into the antibody structure-prediction interface [2023-2]
• MSV is now accessible directly from the protein-protein docking interface [2023-2]
• Selected entries in antibody database management interface can now be exported to MSV and Maestro [2023-2]

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Quantum ESPRESSO: Reduced disk usage with hybrid functionals [2023-2]
• Quantum ESPRESSO: Option to import only the final structure in QE import GUI [2023-2]
• Quantum ESPRESSO: Automatic q-point mesh setup with hybrid functional [2023-2]

Transport Calculations via MD simulations

Product: MS Transport

• Diffusion Coefficient Viewer: Visualization of atoms selected for diffusion tracing [2023-2]
• Viscosity: Expanded range of shear stress available for analysis [2023-2]

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Report of entries with failed predictions if any [2023-2]
• Machine Learning Property: Density prediction for molecular liquids [2023-2]
• Machine Learning Property: Models to measure uncertainties from the predicted properties [2023-2]

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• CG FF Builder: Better defaults for convergence [2023-2]
• CG FF Builder: Option to set initial values [2023-2]
• CG FF Builder: Option to save the force field file in viewer [2023-2]

Dielectric Properties

Product: MS Dielectric

• Complex Permittivity: Option to adjust the length of dipole moment sample extracted from the source trajectory (command line) [2023-2]

MS Maestro Builders and Tools

• Crystal: Edit option for lattice parameters when importing PDB without them [2023-2]
• Manipulate Cell: Option to take multiple entries as input for selected operations [2023-2]
• Meta Workflows: Support for molecular QM simulation stages [2023-2]
• Meta Workflows: Option to compute ESP charges for subsequent stages [2023-2]
• Semicrystalline Polymer: Improved robustness and speed for building semicrystal interface [2023-2]

Classical Mechanics

• Crystal Morphology: Improved pop-up guideline for setting a proper input cell size [2023-2]
• Improved UI to select atoms for substrate restraints in MD-based workflow panels [2023-2]
• Droplet: Option to take existing MD simulation trajectory as input [2023-2]
• Droplet: Support for built-in and custom solvents for contact angle prediction [2023-2]
• Electroporation: Workflow module to simulate and assess membrane electroporation [2023-2]
• Evaporation: Redesigned UI for the workflow setup panel [2023-2]
• Evaporation: Support for evaporating multiple solvents [2023-2]
• Evaporation: Added flexibility to evaporation zone definition [2023-2]
• Evaporation Results: Load structures from one or more iterations into the Project Table [2023-2]
• MD Multistage: Support for negative external electric field [2023-2]
• MD Multistage: Option to remove center of mass velocity [2023-2]
• Stress Strain: Support for sinusoidal loading (command line) [2023-2]

Quantum Mechanics

• Adsorption Enumeration: Option to set bridging and hollow sites for adsorption [2023-2]
• Complex Enumeration: Report of the ligand exchange stability in Project Table [2023-2]
• Prediction of singlet excitation energy transfer rates (SEET) (command line) [2023-2]

Education Content

• New Tutorial: Calculating Voltage Curves on Spinel Intercalation Compounds [2023-2]
• New Tutorial: Machine Learning for Ionic Conductivity [2023-2]
• New Tutorial: Electroporation [2023-2]
• Update: Evaporation [2023-2]
• Update: Droplet Contact Analysis [2023-2]
• Update: Viscosity [2023-2]
• Update: Machine Learning Property Prediction [2023-2]

LiveDesign

What’s New in 2023-2

Kubernetes versions of LiveDesign include:

• Composite Rows
  • Create relationships between entities to better view the composition of complex mixtures, linking them as subcomponents and showing them as indented rows.
  • Get a better understanding of drug formulations by viewing the components that make up the mixture
  • Better define the composition of stereoisomeric mixtures
  • Analyze the differences between different battery electrolyte formulations

All versions of LiveDesign include:

• Forms
  • Show data in a custom, dense arrangement with the Matrix widget
  • Search for compound IDs directly in the Compound Image widget
  • Set up forms more quickly, and identify columns to add to widgets more quickly, with an updated column shuttle
  • Collapse or expand all swimlanes in Kanban widgets using a menu option
  • Form widget titles automatically expand to show longer widget titles when a single widget is within a window
• View any custom Experimental Metadata in the assay tooltips
  • Any metadata can be added to LiveDesign from corporate assay capture systems through the Data Integrator
• Generic Entity – store, model, and analyze any kind of modality in LiveDesign
  • Purge and Overwrite experimental data
  • Append new data to a Lot
• 3D Visualizer
  • View halogen bond and salt bridge interactions
  • Show Chain ID in the residue label
• Significant improvements to streamlining integration of Maestro sessions and LiveDesign servers
  • Benefit from visual notice in Maestro of connected LiveDesign servers, user account recall, and automatic connection to LiveDesign with valid single sign-on
• UI and UX Improvements
  • Independently size column groups and column headers in the LiveReport spreadsheet view
  • View column metadata in tooltip by hovering over a column title in the spreadsheet
  • View the true data point color in Plots after selecting data points
  • Expand and collapse the plot legend to avoid obscuring data points
  • Remove compound images from Plot tooltips
  • Resize columns in the Assay Data Viewer tool
  • Switch between row-per modes more easily
  • Use angle bracket and ampersand characters in formulas for manipulating strings, such as the split() formula
  • Importing compounds through a file and matching by IDs will now skip rows that do not have a match, and report which IDs failed to import

What’s Been Fixed

• Cell coloring rules no longer extend beyond the edge of a tile
• Data & Columns tree tooltips show the correct “View” button or “Edit” button for columns, based on each users’ assigned permissions
• Date and Datetime display formats set within the Admin Panel now apply to all users with a role set to ‘User’
• Editing a picklist Freeform column value in a Kanban widget will immediately update the tile’s location within the Kanban widget
• Filter conditions for formula columns that include substructure images will correctly show the substructure images
• Filter conditions on columns that have file attachments no longer show file IDs in the suggestion dropdown
• Forms correctly show a pointer cursor instead of a grab cursor when viewing the form
• Forms now support drilldown from Kanban widgets to Spreadsheet and Table widgets
• Forms now support multiple instances of the same custom tool
• Histogram and Pie plots permit creating a defined number of equally distributed bins
• Histogram plots within Forms now permit defining custom bins
• LiveDesign will start even if the preprocessor config includes unsupported fields
• MPO desirability cell borders no longer show a color when the color is defined by a proxy value
• MPO tooltips now appear in Form widgets that have a drilldown selection
• Picklist Freeform columns now permit bulk copying dates from assay columns
• Plots that use the Highlighted Substructure column will now show compound images when defining custom bins in Histogram and Pie charts
• Plots with a regression line will correctly scale when the plot axes are converted to log scale
• Plots with log axes no longer show negative values
• Reagents with numeric IDs will correctly carry through their data when used within Reaction Enumeration
• Scatter plots with three axes and many data points no longer show blank exports
• Selecting a range of tiles in a Kanban widget, while holding down the shift key on the keyboard, will now only select the visible tiles within a vertical
• The maximum number of data points allowed within a plot, set within the Admin Panel, now applies to all users with a role set to ‘User’
• Toggling to different plot tabs in Forms will now show the correct data point tooltips
• Typed text within filter conditions, that has not been saved, is now removed after selecting an option from the dropdown list