Release Notes

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