Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Create and share custom visualization Presets  [2022-4]
• Added support to mutate DNA/RNA to standard nucleobases  [2022-4]
• New Workflow Action Menu to guide to next steps for Plot Rigid/Relaxed scans [2022-4]
• First full release of the new 2D sketcher [2022-4]
• Get Going with Maestro Video Series added to Documentation [2022-4]

Workflows & Pipelining [KNIME Extensions]

• Includes the latest version of KNIME (v4.6.1) [2022-4]
• The number of matches can now be controlled in the Phase screening node [2022-4]

In LiveDesign:

• When deploying a model the suitable KNIME protocol is chosen automatically and the latest version of the protocol uploaded [2022-4]
• Distribution of calculations is controlled from the model admin page [2022-4]
• Model changes from the LiveDesign Admin page can be preserved when overwriting an existing model [2022-4]
• A new administration node to move, archive and unarchive models [2022-4]

Target Validation & Structure Enablement

Protein Preparation

• Significant speedup when opening the Protein Preparation Workflow interface on Windows [2022-4]
• Reduced verbosity of Protein Preparation Workflow log file by limiting irrelevant CCD bond assignment error notices [2022-4]
• Protein Reliability Report will generate TEST reflections on-the-fly, if not available in provided .cv file, and report RSCC values [2022-4]
• Updated PROPKA to (latest) version 3.4 [2022-4]

Protein X-Ray Refinement

• Introduction of GlideXtal command line tool for automatic ligand fitting in crystallographic electron density maps [2022-4]
• PrimeX minimization is able to use structure factors in CIF format [2022-4]
• In Phenix/OPLS can now remove all entities clashing with crystal mates [2022-4]
• Phenix/OPLS is more robust to missing atoms in standard residues [2022-4]

Cryo-EM Model Refinement

• Beta GlideEM interface for ligand placement into cryo-electron density maps [2022-4]
• GlideEM now accepts gzipped (CCP4, MRC, MAP) files as input [2022-4]

Multiple Sequence Viewer/Editor

• Beta release of Protein Family Alignment and Annotation [2022-4]
  • A new category named ‘Family Feature Calculation’ located in the ‘Other Tasks’
  • Menu exposes protein family alignment and annotation
  • Supports kinase and GPCR Alignments
  • Supports annotation of GPCR regions
• Dendrogram hover tooltip to display distance information [2022-4]

IFD-MD

• Membrane-bound IFD-MD tutorial [2022-4]
• Covalent ligand IFD-MD tutorial [2022-4]

FEP+

• Show user-friendly message when undefined stereochemical centers are introduced [2022-4]
• Improved usability of FEP+ group panel to manage protonation and tautomeric states ensemble – for more accurate ΔΔG predictions [2022-4]

Constant pH Simulations (Beta)

• Improved usability of constant pH simulations for protein pKa calculations with friendly outputs [2022-4]

AutoQSAR

• Added MACCs keys for ligand featurization in DeepAutoQSAR [2022-4]
• Include ElasticNetCV model (strongly l1/l2 regularized linear regression) in DeepAutoQSAR hyper-parameter optimization [2022-4]
• New DeepAutoQSAR command line utility for greater ease-of-use [2022-4]

Desmond Molecular Dynamics

• In Trajectory Plots view Ramachandran plot of Protein Residues [2022-4]

Empirical and QM-based pKa Prediction

• Initial release of Epik 7, a new machine learning based application for fast pKa value and protonation state prediction [2022-4]
  • Epik 7 can also produce a plot giving the populations of states as a function of pH

Solubility FEP (Beta)

• Option to show solubility results in logS unit [2022-4]

Quantum Mechanics

• Calculate ESP charges for excited states under the TDDFT/TDA approximation [2022-4]
• Complete calculations faster with parallel Jaguar calculations on Windows [2022-4]
• New Workflow Action Menu to guide to next steps for Plot Rigid/Relaxed scans [2022-4]
• Over 80 examples of Jaguar input files in documentation [2022-4]

Semi-Empirical Quantum Mechanics

• GFN2-xTB method now available in the Semiempirical Module panel [2022-4]

Biologics Drug Discovery

• To improve protein linker design, the loop database was updated to a new version specifically intended for interdomain linker design [2022-4]
• To expand chemical liability detection, Asp isomerization pattern and free cysteine detection were added to the Reactive Residues interface [2022-4]
• New command-line script for running Protein Interaction Analysis with the ability to export results to csv format [2022-4]
• First full release of Protein Descriptors interface which now supports .mae and .maegz files containing multiple structures [2022-4]
• Copy-paste sequences into Antibody Structure Prediction interface under new “Enter new sequence” option [2022-4]
• Reuse the same input csv file format for batch homology modeling in Antibody Structure Prediction when running from the command line or Maestro [2022-4]
• Added support for ‘keep glycan’ option in Antibody Structure Prediction during batch modeling [2022-4]
• Cysteine scanning panel for disulfide design now supports remote job submission which is useful for running large jobs e.g. using when MD trajectory as input [2022-4]
• Added “Antibody-Antigen” to Interactions scope dropdown [2022-4]
• Get Going with BioLuminate Video Series added to Documentation [2022-4]

Materials Science

GUI for Quantum ESPRESSO

• Quantum ESPRESSO GUI: Option to hide selected atoms [2022-4]
• Quantum ESPRESSO GUI: Upgraded NEB UI for improved UX [2022-4]
• Quantum ESPRESSO: Endpoints saved for NEB mae files at each iteration [2022-4]
• Quantum ESPRESSO: Reduced file size for custom saved NEB setups [2022-4]
• Quantum ESPRESSO: Use of automatic parallelization with GUI support [2022-4]
• Quantum ESPRESSO: -save_failures option for driver (command line) [2022-4]
• Quantum ESPRESSO: -last_only option for qe2mae tool to save the final structure only  (command line) [2022-4]
• Quantum ESPRESSO: HUBBARD options enabled in input *.cfg (command line) [2022-4]
• Quantum ESPRESSO: Automatic restart for long AIMD simulations [2022-4]
• Quantum ESPRESSO: Support for cell volume relaxation [2022-4]

Molecular Dynamics

• Viscosity: ”,” used as the delimiter in CSV output for Einstein-Helfand analysis [2022-4]

Materials Informatics

• Machine Learning Property: Pre-built, validated machine learning models for a selective list of materials properties [2022-4]
• Molecular Descriptors: Report of semiempirical HOMO-LUMO gap [2022-4]
• Molecular Descriptors: Support for plotting molecular orbitals [2022-4]

Coarse-Grained (CG) Molecular Dynamics

• Support for Ewald sums with Martini force field [2022-4]
• CG FF Builder: Option to export the viewer data to CSV [2022-4]
• CG FF Builder: Support for the use of existing trajectory [2022-4]
• Map Atoms to Particles: Option to map selected atoms from the input structure [2022-4]

Penetrant Loading Simulation

• Penetrant Loading: Robust handling of GCMC water models [2022-4]
• Penetrant Loading: Visualization of periodic unit cell for the output structures [2022-4]

MS Maestro User Interface

• Resized Trajectory Analysis task frame in Maestro for better user experience [2022-4]

MS Maestro Builders and Tools

• Complex Builder: Expansion of ligand library [2022-4]
• Disordered System: Option to generate cells with different numbers of molecules [2022-4]
• Elemental Enumeration: Jobs launched to queue instead of running interactively [2022-4]
• Manipulate Cell: Option to translate within -0.5 and 0.5 of the fractional coordinate [2022-4]
• Manipulate Cell: Support for change of lattice dimensions without FF retyping [2022-4]
• Query Bonds: Option to export output to CSV [2022-4]
• Semicrystalline Polymer: Option to use existing crystal (command line) [2022-4]
• Semicrystalline Polymer: Reporting percentage of crystallinity [2022-4]
• Semicrystalline Polymer: Speed-up for building with polymer models [2022-4]

Classical Mechanics

• MD Multistage: Improved estimation of timestep for Martini systems [2022-4]
• MD Multistage: Option to concatenate stages together for speed-up [2022-4]
• MD Multistage: Built-in Martini relaxation protocol suitable for NVT ensemble [2022-4]
• MD Multistage: Option to only write out selected molecules to trajectories (command line) [2022-4]
• Stress Strain: Output CSV updated at each new data point [2022-4]
• Thermophysical Properties: Support for Parrinello-Rahman barostat (command line) [2022-4]

Quantum Mechanics

• Band Shape: Option to add/select implicit solvent [2022-4]
• Organometallic Conformational Search: Option to select conformers after QM calculations (command line) [2022-4]
• Organometallic Conformational Search: Support for custom MacroModel COM files (command line) [2022-4]
• Organometallic Conformational Search: Support for MOPAC (command line) [2022-4]

Education Content

• Get Going with Materials Science Maestro Video Series added to Documentation [2022-4]
• Quick Reference Sheets available from both Documentation and Training webpages [2022-4]
• New Tutorial: Evaporation [2022-4]
• New Tutorial: Machine Learning Property Prediction [2022-4]
• Updated Tutorial: Polymer Electrolyte Analysis [2022-4]
• Updated Tutorial: Computing Atomic Charges [2022-4]
• Updated Tutorial: Activation Energies for Reactivity in Solids and on Surfaces [2022-4]
• Updated Tutorial: Organometallic Complexes [2022-4]

LiveDesign

What’s new in LiveDesign 2022-4

• The number of logins is enforced by a license limit: Users who attempt to log in after the number of available seats have been assigned will be denied access to LiveDesign
• Admins can forcibly log out users: Users can be forcibly logged out by removing their assigned Roles, or by specifying a specific username
• File Import Receipt: Receive feedback on file imports when the file contains errors, and instructions on how to correct the errors
• Sketcher Improvements:
  • Implicit mode sketcher: Quickly switch between editing compounds and selecting a subset of the compound, by clicking directly on the select tools and draw tools
  • Delete an atom by hovering over it and pressing the Backspace key on the keyboard
• Setting a protocol’s parameter to “Set Default” in the admin panel changes all existing models’ parameter to “Set Fixed”
• Interaction Surface within LigandDesigner: view the interaction surface to determine available growth space within a binding pocket
• Copying a single compound from the spreadsheet can be copied in a Mol v3000 format: a server wide setting permits copying a single molecule as either Extended SMILES or Mol v3000. Selecting and copying multiple compounds as once will copy the compounds using a SMILES format
• Freeform column picklist options can be reordered: Editing a Freeform column definition permits reordering the picklist options
• UI Improvements
  • View more tiles on screen in Tile View, which has a much smaller tile size limit
  • View more data in a spreadsheet cell; the “More Available…” message within spreadsheet cells has been replaced with a gradient to indicate additional data is in the cell
  • Users can use Ctrl-Click to easily display results from additional 3D models in the 3D visualizer.
  • Exported compound structure images will now include stereochemistry labels if these are turned on in the spreadsheet.

What’s Been Fixed

• Model columns can now be sorted and filtered when the cell contains both blank values and numeric or string values. Sorting will use the first non-empty value in the cell.
• Advanced searches with multiple Freeform column conditions return the same results even if the condition order is changed
• Compound images no longer show large atom labels when clicking on them within the main spreadsheet
• Project admins can edit all formulas within their projects
• Pinned plot tooltips in the visualize panel will reappear even after switching to another plot or another LiveReport
• Deleted LiveReports cannot be reopened by navigating directly to the LiveReport’s URL
• Pinned plot tooltips in forms update the connecting line when the view is resized
• Pasting multiple values into Filters will, once again, attempt to automatically identify the delimiter, or present an option to select the delimiter, by which to separate values.
• The LiveReport Manager dialog no longer obscures the last LiveReport with a horizontal scroll bar
• Bond angles for attachment points and carbon atoms from R-group decompositions are now displayed as angles of less than 180 degrees, while before they were displayed at a 180 degree angle
• LiveReports with 3D model returns no longer show a red error bar after opening
• Commons-text has been upgraded to patch security vulnerability CVE-2022-42889
• The 3D visualizer uses the high performance GPU on client computers to avoid crashes
• Formula results no longer disappear from the spreadsheet when columns used in the formula are hidden in the LiveReport
• The matched molecular pairs tool no longer fails to parse chiral compounds represented in an Extended SMILES format
• Error messages no longer sporadically appear when models are updated and saved in the Admin Panel

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.

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Significantly improved speed-up of Entry Inclusion/Exclusion performance (~5x faster) [2022-2]
• Improved graphics performance by employing depth peeling on GPUs [2022-2]
  • GPU-accelerated transparent rendering (beta)
  • Ribbon/Cartoon transparency (beta)
• New Preset view facilitating “Binding Pose Comparison” [2022-2]
• Improved support for renumbering Nucleic Acid residues [2022-2]
• Additional flexibility for viewing antibody annotations in the Structure Hierarchy [2022-2]
• Simple deduplication by entry title with new select “First Entry per Title” feature including extensive group support [2022-2]
• Support importing compressed SMILES (*.csvgz) [2022-2]
• New higher contrast for 2D Overlay colors for improved visualization [2022-2]

Force Field

• Added support for perchlorate ions to OPLS4 [2022-2]

Workflows & Pipelining [KNIME Extensions]

• Includes the latest version of KNIME (v4.5.1) [2022-2]
• New input from LiveDesign node capability makes it easier to create KNIME models taking input columns from LiveDesign and store testing scenarios [2022-2]
• Models based on the LiveDesign Column input protocol can now take 3D column(s) as input [2022-2]
• The Import from LiveDesign node now preserves LiveReport column order [2022-2]
• Capability to move models in bulk between folders for streamlined administration [2022-2]

Target Validation & Structure Enablement

Protein Preparation

• Simultaneously optimize ligand and protein tautomer/pka – cmdline only [2022-2]

Multiple Sequence Viewer/Editor

• Ability to export residues and descriptors to comma-separated text file [2022-2]
• Capability to “Zoom to Selected” and “Reset View” added to Dendrograms [2022-2]
• New option added to turn automatic project saving on or off [2022-2]

IFD-MD

• Improved IFD-MD GUI design [2022-2]
• New IFD-MD support for covalent docking and membrane proteins, expanding the domain of applicability to broader targets and ligands [2022-2]

Hit Identification & Virtual Screening

Pharmacophore Modeling

• Capability to undisplay pharmacophore feature labels in Maestro workspace [2022-2]

Ligand Docking

• SMILES ligand representation is now added to CSV output from Glide [2022-2]
• Ability to specify either fraction of ligands or number of ligands to retain and rescore in Active Learning Glide [2022-2]

Lead Optimization

Ligand Alignment

• Improved alignment method when alignment constraints for maximum common substructure (MCS) are requested [2022-2]

FEP+

• New ability for ligands in solvent leg of relative binding FEP to sample more states with new Dihedral Scaling in Advanced Options [2022-2]
• Improved performance modeling Nucleic Acids by adding NaCl salt at specified concentration in Advanced Options [2022-2]
• New `jws` command-line interface to interface with GraphDB jobs [2022-2]

Solubility FEP

• Analyze results of solubility FEP simulations using the full-featured Perturbation Report Panel [2022-2]

Quantum Mechanics

• Added analytic or pseudospectral RI-MP2 energies, gradients, and second derivatives [2022-2]
• PCM implicit solvent method is now compatible with the Jaguar keywords nofail, nops_opt_switch, check_min [2022-2]
• Ability to optionally optimize geometries with qRNN in the VCD/ECD workflow [2022-2]
• Improved SCF convergence for long range-corrected (LRC) functionals [2022-2]
• Capability to view IR/Raman spectra in Spectrum Plot as transmission or absorption [2022-2]

Semi-Empirical Quantum Mechanics

• The NDDO and MOPAC2016 panels have been replaced by new open source MOPAC panel [2022-2]

Medicinal Chemistry

Ligand Designer

• Improved fine control of ligand growth in Growth Space selection [2022-2]

Biologics Drug Discovery

• New Antibody Structure Prediction Interface with improved antibody detection, alignment, and framework search protocols. The interface accommodates non-traditional antibody formats such as bispecifics and provides an intuitive workflow with capability for batch modeling [2022-2]
• New interface for computing protein-specific descriptors consisting of 160 core sequence, structural and surface features, intended for use in liability prediction for biologics [2022-2]
• Ability to export structures from the Protein Interaction Analysis panel into Residue Scanning with a single mouse click [2022-2]
• Added capability to import csv file with multiple antibody sequences for batch antibody modeling [2022-2]

Materials Science

GUI for Quantum ESPRESSO

• Quantum ESPRESSO: User control over convergence parameters for phonon calculations [2022-2]
• Quantum ESPRESSO: Option to load energy cutoffs from pseudopotentials [2022-2]
• Quantum ESPRESSO: Spin polarization, k-point mesh, and Hubbard U settings reported to Project Table [2022-2]

Molecular Dynamics

Transport Calculations via MD simulations

• Diffusion: Calculation of Onsager coefficient (command line) [2022-2]
• Diffusion: Diffusion trace stored from GUI (maximum of 10) [2022-2]
• Diffusion: User control over number of stored traces (command line) [2022-2]
• Viscosity: Plot of Einstein-Helfand viscosity in the viewer [2022-2]

KMC Charge Mobility

• KMC Charge Mobility: Visualization of occupancy overlay in site energy plot [2022-2]

Materials Informatics

• Molecular Descriptors: Calculation of buried volume over all ligands [2022-2]

Coarse-Grained (CG) Molecular Dynamics

• Apply Coarse-Grained Force Field: beta-cyclodextrin as built-in Martini force field [2022-2]
• Import Coarse-Grained Structures: Support for beta-cyclodextrin [2022-2]
• Coarse-Grained Force Field Builder: Results Viewer [2022-2]
• Coarse-Grained Force Field Builder: Estimation of CG site volumes [2022-2]
• Coarse-Grained Force Field Builder: Group overlap specified per SMARTS [2022-2]
• Coarse-Grained Force Field Builder: Option to define beads by multiple SMARTS patterns [2022-2]
• Coarse-Grained Force Field Builder: User specification of particle volumes [2022-2]
• Coarse-Grained Force Field Builder: Separate control over fitting for bonds and angles [2022-2]
• Coarse-Grained Force Field Builder: Speed-up in building FF (up to 5x) [2022-2]
• Coarse-Grained Force Field Builder: User control of job hosts and license management [2022-2]
• Coarse-Grained Force Field Builder: Users control of particle volume [2022-2]

Optoelectronics

• Optoelectronics Active Learning: Optimization with inverse target property [2022-2]
• Optoelectronics Active Learning: Properties plotted per iteration [2022-2]
• Optoelectronics Active Learning: S1 energy, S1-T1 energy gap as targets [2022-2]

Penetrant Loading Simulation

• Penetrant Loading: User control of job hosts and license management [2022-2]

Morphology Predictions

• Morphology: User control of job hosts and license management [2022-2]

MS Maestro Builders and Tools

• Crystal Builder: Support for P 2c 2n space group [2022-2]
• Digitize Curves: Option to not average over points with the same x-axis values [2022-2]
• Disordered System Builder: Immersed option for substrates with periodic structures with two infinitely stretching axes [2022-2]
• Elemental enumeration: Option to transmute to multiple elements [2022-2]
• Polymer Builder: Support for ladder polymers [2022-2]
• Structured Liquid Builder: Support for adding an entry as both counterion and solvent [2022-2]
• Structured Liquid Builder: Option to show partial densities [2022-2]

Classical Mechanics

• Cluster Analysis: Support for parallel execution of analysis [2022-2]
• Cluster Analysis: Exclusion of single-molecule clusters from analysis [2022-2]
• Cluster Analysis: Support for average Rg and eccentricity [2022-2]
• Define Group by SMARTS: Better mapping of atoms to groups for polymers [2022-2]
• Elastic Constants: User control of job hosts and license management [2022-2]
• MD Multistage Workflow: Stage for Martini CGMD [2022-2]
• MD Multistage Workflow: Enabled Average Cell steps after flexible angle barostat simulations [2022-2]
• Molecular Deposition: User control of job hosts and license management [2022-2]
• Polymer Crosslink: User control of job hosts and license management [2022-2]
• Prepare for MD: Quick solvation for a system (command line) [2022-2]
• Prepare for MD:  Significant speed-up for model preparations with systems containing 1000+ molecules [2022-2]
• Prepare for MD: Option to repartition hydrogen mass to enable simulations with longer time steps [2022-2]
• Stress Strain: Reduced usage of disk space [2022-2]
• Stress Strain: Constant lateral pressure mode for residual strain [2022-2]
• Stress Strain: Support for conditional bond breaking (command line) [2022-2]
• Stress Strain: Option to apply cyclic stress strain analysis [2022-2]
• Torsional Profile Analysis: Speed-up for systems without stereochemistry [2022-2]
• Tg: Option to choose between isotropic and anisotropic barostats [2022-2]
• Multiple panels: Support for save and reuse of ASL patterns [2022-2]

Quantum Mechanics

• Adsorption Energy: Support for restart [2022-2]
• Adsorption Energy: Option to preview and modify geometries manually [2022-2]
• Beta elimination: Option to suppress intermediates [2022-2]
• Bond Dissociation Energy: Support for SMARTS bond selection from workspace [2022-2]
• Reaction Workflow: Option to skip eta rotomer generation [2022-2]
• Reaction Workflow: Option to use custom rate constant equations [2022-2]
• Reaction Workflow: Remove duplicate conformations prior to computing Boltzmann averaged properties [2022-2]

LiveDesign

What’s new in LiveDesign 2022-2

• R-groups returned from decompositions can be used in filters and plots to facilitate SAR analysis
  • Apply coloring rules to R-groups in the LiveReport and within plots
  • Create filters to show only a subset of R-groups
  • Change the shape of data points in a plot according to its R-group
• Visualize more data in plots simultaneously
  • Plot tens of thousands of data points at the same time
  • Apply jitter to data points to more easily distinguish overlapping points
• Enable Single Sign On to more easily control access and permissions
  • IdP administrator can now map IdP group attributes to LiveDesign roles for LiveDesign users
  • Optionally use a user-specific IdP attribute to augment group mappings giving specific users extra LiveDesign roles
• Define proxy values for MPO input columns that are missing data, to more easily compare compounds with different missing values
• Automatically create coloring rules for columns that contain strings
• Usability Improvements
  • Tooltips within the Data & Columns tree have been redesigned to show more information
  • A warning message appears for Project Admins when a template is about to be overwritten that they did not author

What’s been fixed

• Toggling stereo annotations on compound images had no effect and always showed the annotations. Now toggling the stereo annotations works.
• Attempting to recalculate an un-run, click-to-run, model showed a flashing square in the cell that would not disappear until the model was run.  Now the “Run” button will appear in the cell when attempting to recalculate an un-run, click-to-run, cell
• Enhanced stereo labels did not appear in compound images for PPT, PDF, and Excel file exports, and now the enhanced stereo labels appear on the images
• Newly created models did not inherit the command type of the protocol, and now inherit the command type
• Enumerated products from reaction enumeration would not appear in the enumeration preview when those products had many atoms, and now they do appear
• Deleted or cleared Freeform column values would remain visible in plots, and now the data point gets removed
• Saving R-groups from a R-group decomposition into a LiveReport would show extraneous columns, and now only shows the R-groups
• Freeform column edits would occasionally fail for published Freeform columns, and now do not fail
• Setting the aggregation mode to “Latest” on an Experimental Assay column would incorrectly show a qualifier on the value, and now shows the correct qualifier
• Editing a formula would append characters to a column name, and now treats the characters as separate from the column name
• Dose-response curves with a large number of values would fail to appear in a LiveReport, and now appear
• Creating a limited assay column with conditions that did not match any experimental data points would prevent future edits to the conditions from matching data points, and now edits will correctly match data points
• Vertical and horizontal overlays on plots did not extend across the full plot, and now extend the entire height and width of the plot
• Duplicating a subset of a LiveReport that included a MPO would show an error message if the input columns were not also selected, and now duplicating a subset of a LiveReport does not require selecting input columns to a MPO
• Exporting a LiveReport to CSV format would fail when LiveReports contained Ligand Designer columns, and now exports succeed
• Coloring rules could not be applied to columns with a Date datatype, and now can have coloring rules applied

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Apple M1 Support [2022-1]
• New 2D Sketcher (beta) [2022-1]
• New Workflow Action Menus [2022-1]
  • Antibody Modeling
• Homology Modeling [2022-1]

Force Field

• Improved accuracy of histidine parameters, particularly in FEP+ prediction of histidine pka’s [2022-1]
• Improved geometries for B-N bond containing compounds [2022-1]
• Up to 10x faster execution of FFBuilder when parameterizing hundreds of ligands through greater job distribution [2022-1]

Workflows & Pipelining [KNIME Extensions]

• New 2D Sketcher node [2022-1]
• Run from LiveDesign [2022-1]:
  • Export to LiveDesign node can export all the structures so model results can be stored in new LiveReport(s)
  • Model output columns can contain files (eg with pdf)
  • Store an executed workflow in a LiveReport column

Target Validation & Structure Enablement

Protein Preparation

• Sped-up hydrogen atom assignment to be o(n) by system size [2022-1]

Protein X-Ray Refinement

• PHENIX/OPLS supports PHENIX 1.20 [2022-1]

Multiple Sequence Viewer/Editor

• Automatically save MSV projects [2022-1]
• Rapid selection of a subset of sequences based on user-defined percent identity or similarity relative to a reference sequence [2022-1]
• Improved ability to save one or more sequences by ‘right clicking’ to export [2022-1]

Protein Homology Modeling

• Selectively download only the PDB BLAST subset of the NR BLAST database for local homology modeling [2022-1]
• New Workflow Action Menu prompts for homology modeling enables single click access to structure quality assessment, reliability reports, additional loop refinement, and sidechain refinement and localized minimization [2022-1]

Hit Identification & Virtual Screening

Pharmacophore Modeling

• New align_multi_cores.py script to align 3D ligands to a reference ligand with multiple disconnected cores [2022-1]

Ligand Docking

• Return SMARTS of the core used when running core constraint docking with MCS [2022-1]
• Input file that generated a Glide grid is saved in the grid archive to improve ease of making changes [2022-1]

Lead Optimization

FEP+

• FEP+ Correlation Plot [2022-1]:
  • Display best fit line and equation of the line
  • Modified reporting to show confidence intervals instead of standard deviations
• Web services [2022-1]:
  • Improved performance when viewing map status

Solubility FEP (Beta)

• Access to trajectory, representative structures, FEP classifiers in the analysis tab [2022-1]
• Web Services will return fmp/fmpdb files instead of mae/csv for analysis [2022-1]

AutoQSAR

• DeepChemAutoQSAR now supports Windows and Mac platforms [2022-1]

FPsim-GPU

• New vendor column in similarity results [2022-1]

Medicinal Chemistry

Ligand Designer

• Ability to specify a max number of enumerated compounds [2022-1]
• Added access to “Vendor ID” details in the Project Table for purchasable compounds [2022-1]

Biologics Drug Discovery

• Antibody structure prediction backend now supports distributed processing facilitating large-scale, high-throughput workflows [2022-1]

Materials Science

GUI for Quantum ESPRESSO

• Atomic constraints propagated to phonon calculations [2022-1]
• Computing phonons for a subset of atoms [2022-1]
• IDPP (image dependent pair potential) algorithm for NEB [2022-1]
• Support for SCA and R2SCAN functionals [2022-1]

Materials Informatics

•  Molecular Descriptors: Speed-up of fingerprint calculations by parallelization [2022-1]
•  Molecular Descriptors: Organometallic descriptors for compounds with no metals [2022-1]

Coarse-Grained (CG) Molecular Dynamics

•  CG Forcefield Builder: GUI for automated force field building [2022-1]

Optoelectronics

•  Active Learning Optoelectronics: Plot for learning curves [2022-1]
•  Optoelectronics Genetic Algorithm: Option to use AutoQSAR and DeepChem models [2022-1]

Dielectric Properties

• Amorphous Dielectric Properties: Option to export data from the viewer [2022-1]

MS Maestro Builder and Tools

•  Crystal Builder: Option to select symmetry equivalent atoms [2022-1]
•  Manipulate Cell: Option to translate to first unit cell for 2 out of 3 axes [2022-1]
•  Manipulate Cell: Option to unwrap surface model within the periodic cell [2022-1]
• Structured Liquid Builder: Workflow action menu (WAM) [2022-1]

Classical Mechanics

• Cluster Analysis: Average cluster size and number of clusters in viewer [2022-1]
• Cluster Analysis: Option to visualize individual clusters [2022-1]
• Crystal Morphology: Estimation of the number of water molecules to solvate a slab (command-line) [2022-1]
• Membrane Analysis: Prediction of bilayer surface roughness [2022-1]
• Molecular Deposition: Default force constant at 500 kcal/mol/A [2022-1]
• Polymer Crosslinking: Speed-up (2x) by optimized simulation workflow [2022-1]
• Remove Molecules: Support for coarse-grained systems [2022-1]
• Stress Strain: User control of job hosts and license management [2022-1]
• Surface Tension: Workflow module to compute surface tension for a single-component system [2022-1]
• Thermochemical Properties: User control of job hosts and license management [2022-1]
• Thermochemical Properties: Option to choose energy recording interval [2022-1]
• Torsional Analysis: Option to plot relative torsion to initial state [2022-1]
• Torsional Analysis: Option to plot torsion distribution over time [2022-1]
• Torsional Analysis: Faster loading with reduced memory consumption [2022-1]
• Torsional Analysis: Support for coarse-grained structures [2022-1]
• Trajectory Density Analysis: No length limit on input ASL [2022-1]
• Trajectory Electrostatic Potential: Visualization module for radial charge profile and electrostatic potential in a trajectory [2022-1]

Quantum Mechanics

• Adsorption Energy: Thermochemical properties stored in CSV files [2022-1]
• Electron Coupling: Parallelization of QM calculations [2022-1]
• Excited State Analysis: Option to cluster by minimum of hole / electron correlation [2022-1]
• Excited State Analysis: Support for using multiple structures as input [2022-1]
• Ligand Stability Analysis: Stability assessment tool for organometallic complexes enumerated with different ligands [2022-1]
• Reaction Workflow: Buried volume data points stored as CSV file [2022-1]

Molecular Dynamics

Transport Calculations via MD simulations

• Diffusion: Visualization of 3D trajectory trace of a diffusing molecule [2022-1]
• Viscosity: Support for Einstein-Helfand viscosity [2022-1]
• Viscosity: Option to add diffusion calculation [2022-1]

LiveDesign

What’s new in LiveDesign 2022-1

• A new compound sketcher has been introduced, which was designed and developed by Schrodinger
• Add a compound to the sketcher by searching for its ID to use it as a basis for future designs
• Gadgets appear in a new location, along the left-hand panel, and can be grouped into categories to facilitate more rapid discovery of the appropriate gadget
• Computational modeling results can be aligned across columns on a per-pose basis, in order to identify related predicted values
• Tooltips can scroll to show long column descriptions when hovering over a column header

What’s been fixed

• MPOs with Freeform column inputs were not editable when copied from one project to another, and now are editable
• Unpublished clustering models showed duplicate values when a LiveReport was copied, and now show a single predicted value
• 3D data uploaded from Maestro would not appear in the Data & Columns tree, if the LiveDesign instance was configured to group experimental assays by concentration, and now will always appear
• Formula columns and Freeform columns could take several minutes to appear in a duplicated LiveReport, and now appear immediately
• The “Publish” button in the column menu of unpublished models would disappear after clicking it, and now will continue to appear
• Protocols that had a parameter set to optional could not have the parameter changed to mandatory, and now permit setting the parameter to mandatory
• LiveReport tabs could not be dragged and rearranged, and now can be dragged and rearranged
• Protocols that were made accessible in a project, and then made inaccessible to that project, would hide all models based on that protocol. The models now continue to appear in the Admin Panel
• Parameterized models would not display the column name in the Admin Panel when a Freeform column was used as the input parameter, and now display the column name
• Asynchronous tasks that took longer than the timeout period of eight days to complete were not canceled, and now are automatically canceled after eight days
• Creating models with optional parameters has an improved user interface