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

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Simultaneously mutate multiple selected nucleotides [2023-1]
• Quickly select “Nucleic Acids” substructures in the Custom Sets editor dialogs [2023-1]
• New Custom Presets functionality [2023-1]
  • Option to export subset of only selected presets
  • Expanded control with “Color by Element (Chain Name Carbons)” option
• Improved “Maestro to PyMOL” capabilities [2023-1]
  • Improved discovery of “Send to PyMOL” option by moving it to the File menu
  • Option to include trajectory data in “Send to PyMOL”
• Preference to “Keep center of rotation fixed while translating” now enabled by default [2023-1]
• Project Table / Entry List improvements [2023-1]
  • Automatically scroll to the original row of a Shortcut Row entry with a double-click
  • Select rows where any of the included entries have atoms selected in the Workspace
• Show/hide pharmacophore feature labels with the Annotations toggle [2023-1]
• BioLuminate [2023-1]
  • Quickly select antibody-related segments such as CDRs, Fab, Fv and others with predefined selection sets
• View, analyze and share molecular vibrations information with new Vibrations panel [2023-1]
  • Easy-to-use playback controls and tight interaction with the Workspace
  • Save frames from vibration frequency animation as 3D structures
  • Communicate with colleagues through exported movies of selected modes

Workflows & Pipelining [KNIME Extensions]

• Support for KNIME (v4.7) added [2023-1]
• Enhanced robustness of the Extract Properties node where new properties can now be included or excluded [2023-1]
• The LigPrep node now reads setting files exported from Maestro [2023-1]
• The new Protein Preparation Workflow node configuration panel is identical to Maestro’s [2023-1]
• Improvements to LiveDesign Import and Export nodes [2023-1]
  • Move beyond ligands and proteins to import any 2D/3D structure into LiveDesign as generic entities
  • Import entire LiveReports into KNIME for analysis

Target Validation & Structure Enablement

Protein Preparation

• Small peptides (< 200 atoms) can now also optionally be capped [2023-1]

Multiple Sequence Viewer/Editor

• Use the Protein Family Alignment feature to align and annotate new sequences to a user supplied reference set for all protein families (beta) [2023-1]
• Generate complement and reverse complement sequences for Nucleic Acid chains [2023-1]

Desmond Molecular Dynamics

• Improvement in performance up to 1.17X (17%) in ns/day throughput realized from collaboration with NVIDIA. The largest speed improvements from running on modern GPUs with small to moderate sized systems [2023-1]

QM/MM (Qsite)

• More robust and reliable minimizations from switching default minimizer from truncated newton to conjugate gradient [2023-1]
• Added support for dispersion-corrected functionals including DFT-B3LYP-D3, DFT-M06-2X-D3, DFT-B3LYP-D3(BJ), DFT-M06-2X-D3(BJ), DFT-wB97X-D, and DFT-B97-D3 [2023-1]

AutoQSAR

AutoQSAR & DeepAutoQSAR

• Normalize numeric additional features to eliminate instability in network training in case of very large or small values [2023-1]

Hit Identification & Virtual Screening

Shape Screening

• Easily restart Shape GPU calculations from the command line [2023-1]

Lead Optimization

FEP+

• Significant performance improvements of up to 1.4X in FEP+ perturbations/day realized from collaboration with NVIDIA. The greatest speed boosts are observed on larger core count GPUs with small to moderate sized systems [2023-1]
• Improved interface usability when handling groups, including how values are applied to maps [2023-1]
• Automatically calculate protomer/tautomer/conformer populations using Epik7 with fep_groups.py script [2023-1]

Quantum Mechanics

• Easily hide and redisplay spectra in the Spectrum Plot interface [2023-1]
• Added support for rSCAN, r2SCAN, and r2SCAN-D3(BJ) DFT functionals [2023-1]
• Added support for thirty-four D4 dispersion corrected functionals [2023-1]

Semi-Empirical Quantum Mechanics

• Switch from MOPAC7.1 to MOPAC2016 calculation engine for Semiempirical interface [2023-1]

Medicinal Chemistry Design

Ligand Designer

• Design for ligand selectivity through visualization of binding site volumes accessible to only one of two receptors and identifying ligands that dock well into only one of two receptors (beta) [2023-1]

Biologics Drug Discovery

• Perform simultaneous back mutations of multiple residues in Antibody Humanization using the CDR grafting workflow [2023-1]
• Quickly select antibody-related segments such as CDRs, Fab, Fv and others with predefined selection sets [2023-1]
• Connect data to structure in Residue Scanning where selecting residues in the Workspace now also selects the residues in the Residue Scanning table [2023-1]
• ‘Crosslink Protein’ interface has been renamed to ‘Protein Linker Design’ to more accurately reflect its purpose. and now includes access to a choice of two loop library databases, one for constructing intradomain linkers and the other for inter-domain linkers [2023-1]

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Quantum ESPRESSO: Improved scalability and versatility of NEB workflow [2023-1]
• Quantum ESPRESSO: Support for RISM-3D (command line) [2023-1]
• Quantum ESPRESSO: Dimer method for finding transition states (command line) [2023-1]
• Quantum ESPRESSO: Option to apply Niggli reduction (command line) [2023-1]

Materials Informatics

Product: MS Informatics

• Machine Learning Property: Boiling point prediction over a range of pressure [2023-1]
• Machine Learning Property: Interactive prediction for up to 10 selected entries [2023-1]

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Improved loading speed for a CG system in trajectory viewer [2023-1]
• CG FF Builder: Warning from *.log for discrepancy in reduced density [2023-1]
• CG FF Builder: Support for force constants with zero angles [2023-1]
• CG FF Assignment: Improved UI for setting reduced density and cutoff distance [2023-1]
• CG FF Assignment: Support for populating reduced density from the FF file [2023-1]
• CG FF Assignment: Warning for CG particles with large differences in radii [2023-1]

Molecular Dynamics

Product: Desmond

• Improvement in performance up to 1.17X (17%) in ns/day throughput realized from collaboration with NVIDIA. The largest speed improvements from running on modern GPUs with small to moderate sized systems [2023-1]

MS Maestro User Interface

• Periodic boundary condition accounted for evaluating “within/beyond” ASL [2023-1]

MS Maestro Builders and Tools

• Manipulate Cell: Option to shift origin [2023-1]
• Meta Workflows: Module for building and running multiple connected workflows [2023-1]
• Polymer: Support for monomers marked by Mark Head and Tail (command line) [2023-1]
• Query Bonds: Zoom to a bond selected in a row from the panel [2023-1]
• Structured Liquid: Expanded list of built-in lipids [2023-1]

Classical Mechanics

• Droplet: Module to predict contact angle of water droplet on a given substrate [2023-1]
• Evaporation: Workflow module to simulate evaporation with molecular dynamics [2023-1]
• Molecular Deposition: Allow to request only one MD per iteration [2023-1]
• Prepare for MD: Option to scale DPD systems based upon the force field [2023-1]
• Prepare for MD: Additional post-processing for Martini 2.x (command line) [2023-1]

Quantum Mechanics

• Complex Enumeration: Support for non-metal center in complex stability analysis [2023-1]
• Macro pKa: Option to assign active atoms in the course of generating tautomers [2023-1]

Education Content

• New Tutorial: Meta Workflow [2023-1]
• New Tutorial: Water Droplet Contact Analysis [2023-1]
• New Tutorial: Liquid Electrolyte Properties: Part 1 [2023-1]
• New Tutorial: Liquid Electrolyte Properties: Part 2 [2023-1]

LiveDesign

What’s New in 2023-1

• Project Overview Landing Page: View summarized landing page information
• Vertical only Kanban: Create a Kanban view using a single picklist Freeform column
• Forms
  • Use keyboard controls with the Compound Image widget to navigate from one compound to another
  • Define independent column widths for each widget
• Generic Entity: Store Lot and Experimental data on any chemical, biological, or material matter with any representation
• New enhancements to existing features, such as:
  • View the regression equation on scatter plots
  • Admins can log out users by removing their assigned Roles, or by specifying a specific username
  • Removing a single enhanced stereochemical AND group with the structure processor now defines the stereocenter as ‘undefined’, and previously would define is as an absolute stereocenter
  • Use advanced atom query features in substructure filtering
• Performance Improvements
  • SAR analysis tasks are performed asynchronously and take less time to complete
  • The 3D visualizer is more responsive when large proteins are viewed

What’s Been Fixed

• Models that returned a single value now show the full result unaligned with other columns
• The 3D visualizer uses the high performance GPU on client computers to avoid crashes
• Pasting multiple values into ID search will attempt to automatically identify the delimiter, or present an option to select the delimiter, by which to separate values
• Limited Assay Columns are now included in Matched Molecular Pairs analyses
• Pasting multiple values into Filters will attempt to automatically identify the delimiter, or present an option to select the delimiter, by which to separate values
• File import receipts show a scroll bar for errors parsing SD files
• Pinned plot tooltips in forms update the connecting line when the view is resized
• The file import receipt now shows IDs from SD file title lines
• Overlay lines in plots will now extend to the full plot dimensions
• Automatically generated coloring rules for R-groups, Scaffolds, and String columns that were created through the plot interface will now appear in plots
• Pinned tooltips now point to the correct data points in box plots
• The radar chart legend now shows which compound IDs are out of range by hovering over the “Out of Range” entry in the plot legend
• Multi-parameter optimization column dialogs appeared to allow unauthorized users to edit the definition, however any edits submitted were not saved. The dialog now shows all fields as disabled to unauthorized users.
• LiveReports set to Read-Only no longer allow users to configure Tile View
• Line charts no longer show R-groups as SMILES strings in the plot legend, and instead show images
• Forms with many narrow widgets not longer show errors when editing the Form
• Dragging to select multiple histogram bars will select all of the compounds within the bin

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.