Release Notes

Small Molecule Drug Discovery

Target Validation & Structure Enablement

Protein Preparation

• Reorganized and grouped Protein Prepwizard command line options for improved clarity and correspondence with the Maestro interface [2022-3]
• Improved valence error reporting in Diagnostics interface [2022-3]
• Several orders of magnitude speedup when assigning zero-order bonds and running the Epik stage in the Protein Prepwizard on large structures such as a ribosome [2022-3]
• Several times faster performance of ProtAssign when running on large structures with many small clusters or structures with a few large clusters [2022-3]
• Addition of -include_ligand_states flag in command line prepwizard and protassign scripts, to include Epik generated ligand states during the hydrogen bond assignment stage [2022-3]

Protein X-Ray Refinement

• Phenix/OPLS: Option to significantly improve computational performance by lowering the nonbonded energy term cutoff [2022-3]
  • A Phenix-side option schrodinger.flags.nonbonded_cutoff changes the cutoff. Default is to not change the cutoff. This has been tested with a cutoff of 10 angstrom, which increases computational efficiency by several times while no penalty to refinement statistics is observed.

Cryo-EM Model Refinement

• Introduced a new mode peptide for GlideEM, for enhanced peptide sampling with the command line parameter -nconformers specifying the number of conformers to generate [2022-3]
  • Additional input conformations are generated by running confgen on the peptide and redocking each conformation. The time and required computational resources required scale linearly with -nconformers
• Binding pocket / docking grid center can now be specified by binding site ASL and the ligand provided in a separate file in GlideEM [2022-3]
  • The binding site can be specified using the new -binding_site_asl command line argument, which requires an ASL that specifies residues near the binding site. The docking grid center will be the geometric mean of all atoms specified by the ASL. The ligand can be provided using the -ligand_struct command line argument

Platform Environment

Maestro Graphical Interface

• Apply styling and change molecular representations on selected entries [2022-3]
• New Workflow Action Menu support for Protein-Protein Docking [2022-3]
• “Send to PyMOL” panel preserves Maestro’s non-bonded interactions when viewed in PyMOL [2022-3]
• Create zero order bonds withing the 2D sketcher [2022-3]
• More reliable selection with improved accuracy of selecting atoms and bonds within the 2D sketcher [2022-3]
• Save user selection of authentication with LiveDesign by either credentials or single sign-on [2022-3]
• New Help icon provides access to relevant tutorials as well as documentation [2022-3]

Force Field

• Improvements to scalability of large FFBuilder jobs [2022-3]

Workflows & Pipelining [KNIME Extensions]

• Schrödinger extensions are compatible with KNIME 4.6 [2022-3]
• Create and apply ML models with new DeepAutoQSAR nodes [2022-3]

Hit Identification & Virtual Screening

ABFEP

• Performance in ABFEP loading [2022-3]

Lead Optimization

FEP+

• Drastically improved interactive performance of FEP+ Analysis tab interface with large maps with 100s of nodes edges [2022-3]
• Correlation plots will show pairwise ddG histogram (previously edgewise was shown) [2022-3]
• State Groupings GUI [2022-3]
  • Tautomers
  • Protomers
  • Conformers (binding poses)

Protein FEP

• Residue Mutation Selection layout change [2022-3]
  • Added support of CYM amino acid (deprotonated Cysteine)

Constant pH Simulations (Beta)

• The pH interval is fixed at 0.5 units and show number of resulting replicas [2022-3]

Solubility FEP

• Experimental ΔG data is shown in Analysis tab if the data is available [2022-3]

Biologics Drug Discovery

• Protein Interaction Analysis
  • Filter protein-protein interaction by residue features, non-bonded interaction types, and interaction distances [2022-3]
  • Buried solvent-accessible surface area and surface complementarity of interface residues reported in results table [2022-3]
  • Select, display and style only interface residues in interaction analysis panel [2022-3]
• Residue Mutation
  • Enhanced performance of residue scanning from Maestro, enabled hundreds of thousands of mutations to be examined simultaneously [2022-3]
  • Mutated residue name added as as property in the residue scanning output structure to facilitate downstream analysis and workflow scripting [2022-3]
• Protein-Protein Docking:
  • Guidance on common next steps provided following PIPER docking through the Workflow Action Menus  [2022-3]
• Antibody Loop Modeling
  • Specify numbering scheme, and thus loop definitions, prior to running PRIME loop refinement including Chothia, Enhanced Chothia, Kabat, IMGT and AHo [2022-3]

Materials Science

GUI for Quantum ESPRESSO

• Effective Screening Medium: Option to align structures in GUI from selected entries [2022-3]
• Quantum ESPRESSO: Support for runner.py to run TDDFPT [2022-3]
• Quantum ESPRESSO: Restart option for ab initio MD (command line) [2022-3]
• Quantum ESPRESSO: Support for slab models with custom dimensionality [2022-3]
• Quantum ESPRESSO: Upgrade to Quantum ESPRESSO 7.1 [2022-3]

Molecular Dynamics

Transport Calculations via MD simulations

• Viscosity: Thermostat and barostat settings (command line) [2022-3]

Coarse-Grained (CG) Molecular Dynamics

• CGFF Builder: Better estimation of particle volume prediction using atomistic structures [2022-3]
• CGFF Builder: Option to set common mass for all particles. [2022-3]
• CGFF Builder: Implicit charges stored in the FF file and reported in the viewer [2022-3]
• CGFF Builder: Option to import saved SMARTS pattern [2022-3]
• CGFF Builder: Default bond-length bounds adjusted by the cutoff [2022-3]
• CGFF Builder: Each CG-mapped molecule type saved as a copy [2022-3]
• Viscosity: Automatic setup of thermostat and barostat for CG systems [2022-3]

Optoelectronics

• AL OptoE: Expanded property space for optimization [2022-3]

Dielectric Properties

• Complex Permittivity: Improved UI to show permittivity for specified frequency [2022-3]
• Complex Permittivity: Separate visualization of storage and loss functions [2022-3]

MS Maestro Builders and Tools

• Nanostructure: Periodicity of the output structures set by default [2022-3]
• Polymer: Template for Chitosan and Xanthan Gum under Carbohydrates [2022-3]
• Polymer: Hydroxyl group as the default terminator for carbohydrates [2022-3]
• Semicrystalline Polymer: Support for running on multiple hosts [2022-3]

Classical Mechanics

• Molecular Deposition: Preview of the number of MD stages [2022-3]
• MD Multistage: Temperature control in brownian stage [2022-3]
• MD Multistage: Relaxation protocol for stiff polymers [2022-3]
• Polymer Crosslink: Option to store and recall SMARTS patterns [2022-3]
• Polymer Crosslink: Option for SMARTS search method (command line) [2022-3]
• Stress Strain: Option for SMARTS search method (command line) [2022-3]
• Stress Strain: Speed up (up to 2x) of cyclic stress strain jobs [2022-3]
• Stress Strain: Preview of total simulation time from the GUI [2022-3]
• Surface Tension: Support for long-range cut-off [2022-3]
• Surfactant Tilt: Improved UI for surfactant selection [2022-3]
• Trajectory Density Analysis: Improved UI for trajectory range setup [2022-3]

Quantum Mechanics

• Adsorption Enumeration: Option to position adsorbate distanced from the substrate [2022-3]
• Excited State Analysis: Support for custom definition of fragment [2022-3]
• QM Multistage: Option to turn off robust convergence [2022-3]
• Ligand Exchange: Report of detailed progress in the driver log [2022-3]
• Automatic spin treatment as default for Jaguar Options within QM panels [2022-3]
• Reaction Workflow: Support for geometry deduplication [2022-3]
• Reaction Workflow: Support for η- or centroid- representation for output [2022-3]
• Reaction Workflow: Support for specifying R-group enumeration sites [2022-3]

LiveDesign

What’s new in LiveDesign 2022-3

• Machine Learning: Predict properties by building and using DeepAutoQSAR and a model management tool
• Kanban layouts: Visualize and manage workflows, projects, and synthesis queues
• View all assay data for a compound: Query all assay data for a compound by using the Assay Data Viewer tool
• Matched Molecular Pairs: Perform a matched molecular pairs analysis by querying precomputed datasets or generating analyses on-the-fly, and analyze multiple properties at once
• New enhancements to existing features, such as:
  • Configure models to use options from a picklist
  • Plot multiple experimental values for a single compound
  • Updated plot legend that no longer overlays the plot
  • View drop down suggestions that are specific to the LiveReport in Filters, Coloring Rules dialogs, and MPO Configuration dialogs
  • Switch modes in the Sketcher by using the keyboard’s spacebar
  • Ligand Designer allows for more simultaneous users due to more rapid license checkout and return
  • Compound images show heteroatoms that are proportional to bond lengths
  • Hide tabs on Forms widgets to improve screen real estate usage
  • Updated tooltips for experimental values, which can open the Assay Viewer tool to inspect experimental metadata
  • Automatically generate coloring rules based on row selection for categorical columns
• New performance improvements that speed up advanced search, speed up sorting, and speed scrolling in LiveReports with many columns
• Workflows & Pipelining [KNIME Extensions]
  • When deploying a model the suitable KNIME protocol is chosen automatically and the latest version of the protocol uploaded
  • Distribution of calculations is controlled from the model admin page
  • Model changes from the LiveDesign Admin page can be preserved when overwriting an existing model
  • A new administration node to move, archive and unarchive models

What’s been fixed

• Column tree search terms and results are now resetting upon clicking cancel on a dialog and accessing again.
• Tile View header names  for unpublished columns use a hash background for the entire cell, while before it was only used for the text itself.
• A format inconsistency when a Tile includes a 3D column has been fixed.
• The “Unfreeze all rows” message now disappears once clicked from other views than spreadsheet, while before it was persisting.
• Global templates can now be applied to an existing LiveReport.
• The display of the tooltip of the Save button for Landing Page bookmarks has been fixed.
• In the LiveReport picker, selection is now kept if the creation of a new folder is aborted.
• LiveReports including MPO can now be copied to other projects.
• Project picker does not persist anymore if a user navigates to a LiveReport using its URL.
• Date field values of Landing Page bookmarks are now validated. An incorrect value will trigger a warning message.
• Template search on Landing Page is now case insensitive.
• MPO tooltip now properly displays all constituents information even for constituents not present in the current view.
• MPO tooltip position was not consistent depending on the presence of a proxy value score. It now is.
• MPO score now appropriately reflects the change of a previously defined constituent that is changed to a null value.
• Legend now pops out with a chart when not attached.
• Plot legend is now appropriately repositioned upon screen resolution changes.
• Box Plots now supports a larger number of data points.
• Export to image of line plots split by series with a large amount of data now include all data points as expected.
• Histogram and Pie plot tooltips now show decimal separators as per the server setting.
• In the Firefox browser, user axis font size is now taken in account while it was ignored before.
• The warning message indicating that the number of allowed points in a plot has been exceeded is now properly displayed. In particular it is not hidden anymore by the message offering to activate Jitter functionality in scatter plots.
• When exporting plots to images, data points now have borders, preventing points without color to not be displayed in the image.
• Sgroup annotations of abbreviated functional groups for structure imported in v2000 CTAB format are now properly displayed.
• The property RDKIT_STRUCTURE_PROCESSOR_SGROUP_FIELD_NAMES, which defines which Sgroup fields should be considered as part of registration, is now properly taken in account.
• R-group Decomposition now matches tautomers when “RDKIT_TAUTOMER_SEARCH” is set to true.
• First click on the sketcher now focuses the input, while before it was adding a CH4 to the sketch.
• Fix an issue impacting the sketcher display after successive change of the size and/or minimization of the browser window.
• Upon upgrade, the new version of the sketcher does not require a hard refresh of the page orto clear the browser cache.
• Dragging a compound into the sketcher, and then adding a ring or bond, will show a proportionally sized ring or bond.
• Advanced searches with an inverted “Presence in LiveReport” now return results.
• Freeform columns that are hidden in the LiveReport now appear as options for the Kanban widget.
• The kanban widget now shows tiles in edit mode after configuring the widget.
• R-groups can now be added to the LiveReport via the sketcher.
• Uploading unpublished data from Maestro, and then re-uploading that data as published to the same LiveReport, now shows those columns in the Data & Columns tree.
• Hidden columns now appear in the file export when they are explicitly selected.