Schrodinger Suites 2024-4

Small Molecule Drug Discovery

Platform EnvironmentTarget

Maestro Graphical Interface
- Improved usability in scatter plots and histograms:
. See relationships in data across multiple plots and histograms with streamlined menu into “Entry Actions” and “Sync Options” menu icon
. Added support for string and boolean histograms
- In the histogram panel, easily switch between settings and data table views
- Specify the number of columns and rows for fine control of Workspace Tiles
- Save animated GIF of vibrational motion from Jaguar frequency calculation
- Enhanced Cryo-EM surface performance:
. Up to 2x faster loading of Cryo-EM surface files
. Up to 5x increase in speed for isosurface contour creation and adjustments
- Refined toolbar design for enhanced simplicity, modern aesthetics, and optimization for dark mode
- Updated Maestro Project format to version 5:
. Support for multi-letter chain names beyond traditional 26 characters
. Compressed .prjzip files designed for easy sharing via email
. Automatic conversion of version 4 projects to version 5 upon opening
. By default save Maestro Projects in version 5 format with an option to save in version 4 for backward compatibility
- Support added for two new CIF file formats: “PDBx/mmCIF (*.cif)” and “Small Molecule CIF (.cif)”
- Opening Maestro locally from LiveDesign is now supported on macOS, Linux, and Windows
- Revamped splash screens & iconography: Modern visuals for an updated look and feel
Workflows & Pipelining [KNIME Extensions]
- LiveDesign Admin node can take user credentials from the LiveDesign Connection node enabling SSO configuration

Target Validation & Structure Enablement

Protein Preparation
- Protein The Protein Preparation Workflow now considers Epik states of ligands during the hydrogen-bond network optimization stage by default
Protein X-Ray Refinement
- New sf2map.py script quickly generates an aligned x-ray map, given an input structure and a cif file containing structure factors
IFD-MD
- Updated IFD-MD for automatic sampling of histidine tautomer states (HID, HIE): Consider induced fit effects simultaneously to resolve receptor tautomeric states and predict receptor and ligand conformations

Binding Site & Structure Analysis

SiteMap
- Automatically apply Combined Mode which breaks down sites larger than 800 Å3
Mixed Solvent MD (MxMD)
- Improved cryptic pocket identification with new mixed solvent molecular dynamics (MxMD) interface including customizable visualization (Beta): Gain a clearer understanding of candidate binding pockets on the protein surface with a new interface to set up and analyze MxMD simulations

Hit Discovery

Active Learning Applications
- Faster time-to-results in AL-Glide and Glide using ZeroMQ mode for machine learning evaluation stage and Glide docking stage
Shape Screening
- Additional similarity normalization schemes now available for Quick Shape and 1D Screening command. In addition to the max{O(A,A), O(B,B)} default can apply min{O(A,A), O(B,B)}, O(A,A), and O(B,B) where O(A,B) is the overlap between ligands A and B
- Run Quick Shape and 1D Screens against a Phase pharmacophore hypothesis as the query
- Improve speed of Quick Shape calculations with -limit and -NJOBS1D options that enable more efficient utilization of compute resources
Glide
- Full release of Glide WS mode, previously known as WScore, to prioritize ligands for improved hit enrichment and pose prediction accuracy
. Leverages explicit water energetics to enhance the accuracy of protein-ligand poses and reduce experimentally inactive compounds in top-scoring virtual hits

Lead Optimization

FEP+
- Gain deeper insights into receptor-ligand interactions with new Per-Residue Energy Decomposition in FEP Edge analysis
- Perform categorical analysis in the Correlation Plot (FEP+) interface using classification matrices including common metrics such as Accuracy, Specificity, Recall, Precision, F1 Score, Cohen’s K and Kendall’s T
- View reason why compounds are skipped in ABFEP calculations in the FEP+ Panel
Protein FEP+
- Full release of Protein FEP+ Residue Scanning (with lambda dynamics)
. Workflow now generates an FMP archive to be loaded in the FEP+ Panel
. Web Services support
FEP Protocol Builder
- Ability to run with either OPLS4 or OPLS5 force field
- Added support for sampling of more residue protonation states
- New option to skip active learning and perform exhaustive exploration of protocol parameter space
Quantum Mechanics
- Return solvation entropy in implicit solvent calculations
- distributed_frequencies.py workflow for numerical frequency calculations
- Added support for isotope 11B in NMR calculations
- Implicit solvent model SMD now has gradients and frequencies
- E-sol now supports the CPCM-X implicit solvation method for rapid solvation energies (command line only)
Semi-Empirical Quantum Mechanics
- Updated xTB to version 6.7.1 which uses the advanced solvent model CPCM-X
Macrocycles
- Expanded list of predefined linkers from 5 to 22 for small molecule cyclization in macrocycle.py
- Expanded list of side-chain bridges for peptide cyclization from 4 to 21 of the most commonly reported in the literature
- Control spacers in macrocyclize.py via a CSV file of SMILES strings
- Improvements to macrocycle alignment reproducibility and performance in tug_align script and Ligand Alignment Panel
- Macrocycle sampling script can optionally output only macrocycle conformers
- Easily create cyclic peptides from sequence on the command line with peptide_cyclize.py script

De Novo Design

AutoDesigner – R-group Design

- Boost exploration of similar ligands with new AutoDesigner Similarity feature that scores output ideas based on similarity to a user-provided set of compounds
- Added exhaustive PathFinder enumeration of all routes of the starting ligand using all available building blocks for those routes
- Added recursive trimming of the final set of outputs to generate additional outputs
- Improved logging including an overview of the number of compounds generated at various stages of the workflow

AutoDesigner – Core Design

- Improved logging including an overview of the number of compounds generated at various stages of the workflow

Biologics Drug Discovery

- Predict protein properties with automated machine learning model building using protein descriptors: Leverage AutoQSAR analysis to train, validate, and apply AI/ML models for biologics properties prediction
- Predefined selection sets for quick access to TCR regions like CDRs, alpha/beta chains, and more

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

- Phonon-dependent dielectric properties reported in the Phonon DOS viewer
- Workflow action menu (WAM) for NMR calculations
- Support for phonon calculations with DFT-D3
- Improved cell relaxation protocol
- Schrödinger-compatible Quantum ESPRESSO releases available at Github
- Support for distributed phonon calculations
- Control over maximum number of retries after failure via config file (command line)
- Initial parameters and constraints preserved in the QM Convergence Monitor

KMC Charge Mobility

Product: MS Mobility

- Compute KMC Charge Mobility: Improved speed with robust QM convergence (command line)

Materials Informatics

Product: MS Informatics

- Formulation ML: Increased number of available steps for hyperparameter tuning
- Formulation ML: Option to replace hyperparameter tuning steps with training time
- Formulation ML: Visualization of atomic contributions from the feature importance analysis
- Machine Learning Property: Updates to existing models
- Machine Learning Property: Prediction of melting point for molecular solids
- Machine Learning Property: Prediction of non-aqueous solubility of molecules

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

- Automated CG Mapping: Speed up for mapping large molecules
- Automated CG Mapping: Particle types and the number of occurrences reported

Penetrant loading simulations

Product: Penetrant Loading (PL)

- Penetrant Loading: Differentiation between pre-existing water and added water

Reactivity

Product: MS Reactivity

- Nanoreactor: Option to set the width of the biasing potential
- Reaction Workflow: Anharmonic zero point energy (ZPE) added to Project Table
- Reaction Workflow: Support for enumeration on sites in rings
- Reaction Workflow: Option to automate the swap fragment with enumeration
- Reaction Workflow: Preview of reaction diagram at the setup

Microkinetics

Product: MS Microkinetics

- Microkinetic Modeling: Support for multistage MKM analysis
- Microkinetic Modeling: Support for zoom in on plots in the viewer panel
- Microkinetic Modeling: Increased default value for maximum integration time step
MS Maestro Builders and Tools
- Adsorption Enumeration: Support for selection of reactive atoms by atom indices
- Disordered System: Improved UI with reconfigured options for tabs and dialogs
- Disordered System: Support for keeping selected molecules rigid with tangled-chain option
- Meta Workflows: Support for radial distribution function analysis
- Nanoparticle: Option to include only molecules with center of mass inside the particle
Classical Mechanics
- Barrier Potential for MD: Option to remove barrier from input structures
- Droplet: Support for entering random seed in building a droplet
- Droplet: Support for randomized initial velocities
- Evaporation: Support for full control over which profiles to plot
- Evaporation: Support for applying barrier potentials
- Evaporation: Option to set evaporation zone based on the distance from COM of the substrate
- Evaporation: Improved loading speed for large input structures
- MD Multistage: Improved relaxation protocol for ladder polymers
- Refined default timestep for DPD particles
- Thermostat and barostat settings set automatically for atomistic and coarse-grained systems
- Stress Strain: Option to plot normal average stress
- Thermophysical Properties: Option to return *.ene files (command line)
- Trajectory Density Analysis: Output *.csv files
Quantum Mechanics
- Adsorption Energy: Option to select between kcal/mol and kJ/mol for energy units
- Adsorption Energy: All output entries incorporated in Project Table as subgroups
- Adsorption Energy: Robust detection algorithm for valid input adsorbates
- Adsorption Energy: Support for loading options from a Quantum ESPRESSO config file
- Optoelectronic Film Properties: Prediction of molecular refractive indices
- Optoelectronic Film Properties: Prediction of intersystem and reverse intersystem crossing rates
- Optoelectronic Film Properties: Improved loading protocols for large input structures

Education Content

Life Science
- New Tutorial: Protein pKa Prediction with Constant pH Molecular Dynamics
- Updated Tutorial: Glide WS Evaluation of HSP90 Ligands
Materials Science
- New Tutorial: Singlet-Triplet Intersystem Crossing Rate
- New Tutorial: Modeling the Formation and Decomposition of Nitrosamines
- New Tutorial: Atomic Layer Deposition
- New Tutorial: Elemental Enumeration
- New Quick Reference Sheet: Refractive Index
- Updated Tutorial: Introduction to Multistage Quantum Mechanical Workflows

Docs Content

- New documentation page to explore solutions for materials science applications and to identify the best fit for users’ interest
- Panel images shown in the help topic of each panel

LiveDesign

What’s upcoming in 2024-4
- Biologics SAR Visualization: View, highlight, and analyze properties alongside sequence differences in the Sequence Viewer tool
- Ligand Designer: Upload multiple overlays and rename docked poses for tracking
- R-group enumeration: Filter output products by computed properties to enumerate a set of products within a defined chemical space
- Updated LiveReport Picker: View row, column, and cell count for LiveReports in the LiveReport Picker to quickly identify LiveReports that are candidates for deletion