Release Notes

Small Molecule Drug Discovery

Platform Environment

Maestro Graphical Interface

• Dynamically display measurements based on selected atoms in the Status Bar
• Copy fragments from existing molecules in the 3D Workspace and paste them onto selected atom(s) in another molecule
• Export movies from the Trajectory Viewer with the Workspace resolution
• Search in the Entry List using regular expressions for greater precision. Simultaneously search for multiple structures
• Aligned pharmacophore label font with Maestro font preferences
• Display T-cell receptor annotations in the Structure Hierarchy
• Automatic synchronization of data point selection in scatter plots with Project Table selections and/or Workspace inclusion
• Display data from different groups in a single scatter plot

Force Field

• New OPLS5 Force Field: Significant improvement in the accuracy of cation-pi interactions and polarizable and ionic group interactions via the addition of limited polarizability via OPLS5 in relative binding-FEP+ and Desmond (beta)

Workflows & Pipelining [KNIME Extensions]

• Supports the latest version of KNIME (v5.2)
• The Chemistry external tool node supports a new FEP+ column type that points to fmp files read by the FEP+ reader node

Binding Site & Structure Analysis

SiteMap

• More accurate identification of RNA binding sites with 89% of RNA sites in HARIBOSS set now identified as the top-ranked binding site by SiteMap, up from 69% previously (beta)
• New SiteMap parameters to separate large pockets that are bleeding into one another or across the protein surface and identify smaller distinct sites (command line only)

Mixed Solvent MD (MxMD)

• Support for membrane systems

Hit Identification & Virtual Screening

Ligand Preparation

Active Learning Applications

• Enhanced diversity selection in AL-Glide through consideration of up to 3x more compounds by horizontal scaling of diversity selection
• Significantly improved LigandML prediction throughput in AL-Glide through use of ZMQ (command line only) (beta)
• Much faster file uploading to the DriverNode in AL-Glide (command line only) (beta)

Ligand Docking

• Improved pose-prediction and enrichment when docking small molecules into RNA receptors with Glide (beta)

Lead Optimization

FEP+

• Support setting up Positional Restraints in RB-FEP via FEP+ panel
• Ability to use OPLS5 for Increased RB-FEP Accuracy
• Improved Trajectory Management allowing trajectories from multiple edges in PT

Protein FEP

• Support of Multi-Site Mutations for Thermostability prediction

Constant pH Simulations

• Support of Lys pKa Calculations with panel support

Solubility FEP

• Improved Trajectory Visualization
• Link to Best Practices document
• Support of Force Field Builder from Web Service

FEP Protocol Builder

• Use FEP Protocol Builder to quickly identify FEP+ model parameters that optimize FEP+ accuracy using an automated machine learning-driven workflow
  • Free researcher time by letting the FEP Protocol Builder explore parameter space to identify and visualize optimal parameters for FEP+ model performance
  • Find FEP models for challenging systems through efficient exploration of parameter space
  • Proceed with confidence to use FEP+ prospectively in your program
  • Interface to set up FEP protocol optimization calculations with automated assignment of ligands into test/training sets
  • Interface to analyze influence of parameters on FEP model performance and compare protocol performance via FEP+ correlation plots

Quantum Mechanics

• Perform wave function stability analysis in Jaguar
• Generate NMR chemical shifts and spectra of 19F isotope with Jaguar Spectroscopy
• Set multiplicity automatically (multip=2) if an odd number of electrons are found in Jaguar
• Search for atropisomers using the new rotation_barriers.py script (command line only)
• More robust and performant E-sol workflow suitable for LiveDesign and command line execution 
• Modify level of theory and basis sets of multiple entries with a right mouse click

Medical Chemistry Design

Ligand Designer

• New Ring Swapping workflow to optimize lead compounds by exploring alternative ring scaffolds (beta)

Biologics Drug Discovery

• Added 430 new non-natural amino acids to the library for use in peptide design
• Interface improvements to speed analysis of protein mutation results produced by residue scanning
• Analyze structural ensembles such as PIPER docking results and MD trajectories  with Protein-protein interaction analysis panel (open beta)
• New option to specify one of five numbering schemes, Chothia, Kabat, IMGT, Enhanced Chothia or AHo, when performing antibody structure alignment using the align_antibody.py script

Materials Science

GUI for Quantum ESPRESSO

Product: Quantum ESPRESSO (QE) Interface

• Input for magnetization from structure data (command line)
• Results viewer for solid state NMR spectra
• NEB Convergence Monitor: Display of relative / activation energies
• Automatic shift of K-point grids for improved convergence
• Option to compute and visualize potential surfaces in the workspace
• Phonon Density of States Viewer: Support for dielectric constant
• Speed-up of NEB calculations with smart management of wave function data

KMC Charge Mobility

Product: MS Mobility

• Compute KMC Charge Mobility: Charge transfer computed based on center-of-mass distances

Materials Informatics  

Product: MS Informatics

• Formulation ML: Support for input data with missing component names / SMILES
• Formulation ML: Support for Set2Set and graph-based models and descriptors added
• Formulation ML: Option to remove highly-correlated descriptors (command line)
• Formulation ML: Option to control the training set size
• Formulation ML: Support for classification mode
• Formulation ML: Feature-importance analysis based on Shapley additive explanations (SHAP)
• Machine Learning Property: Improvements in prediction models available for download
• Machine Learning Property: Prediction of oxidation and reduction potentials
• MD Descriptors: Support for formulations-focused descriptors

Coarse-Grained (CG) Molecular Dynamics

Product: MS CG

• Coarse-Grained Force Field Builder: Automatically map atomistic systems to Martini particles (command line)
• Coarse-Grained Force Field Builder: Fit Martini parameters (command line)

Reactivity

Product: MS Reactivity

• Nanoreactor: Improved default settings
• Nanoreactor: Speed-up of xTB frequency calculations
• Nanoreactor: Improved deduplication algorithm for products
• Nanoreactor: Improved parallelization algorithm
• Nanoreactor: Option to remove high-energy products
• Nanoreactor: xTB free energy used to rank-order products
• Auto Reaction Workflow: Prevention of excessive equilibrium constant calculations from permutations

Microkinetics

Product: MS Microkinetics

• Microkinetic Modeling: Support for the use of analytical Jacobian
• Microkinetic Modeling: Option to specify collision factor
• Microkinetic Modeling: Results returned for cases that did not reach a steady state
• Microkinetic Modeling: Option to list chemical equations from the input reaction network

Reactive Interface Simulator

Product: MS RIS

• Solid Electrolyte Interphase: Reaction-template based solution for dynamic simulations of materials systems near battery electrodes

MS Maestro Builders and Tools

• Density Profile: Visualization of density isosurfaces
• Complex Builders: Option to clean up geometry using xTB
• Semicrystalline Polymer: Support for polyvinyl alcohol (PVA)
• Solvate System: Protocol to manage output with more than 2M atoms
• Structured Liquid: Protocol to manage output with more than 2M atoms
• Structured Liquid: Improved and expanded built-in lipid library

Classical Mechanics

• Thermal Conductivity: Solution to predict thermal conductivity of solids

Quantum Mechanics

• Adsorption Enumeration: Improved algorithm to define surface atoms
• Adsorption Enumeration: Heavy-atom filter for reactive atoms
• Amorphous NMR: Isosurface data available from QM calculations

Education Content

Life Science

• New Tutorial: Ligand Binding Pose Prediction for FEP+ using Core-Constrained Docking (NEW)
• New Tutorial: Ligand-Based Virtual Screening Using Phase (large-scale rework from the ground up)

Materials Science

• New Tutorial: NMR Spectra Prediction
• New Tutorial: Thermal Conductivity
• New Tutorial: Solid Electrolyte Interphase Calculations
• New Tutorial: Building a Semicrystalline Polymer
• Updated Tutorial: Machine Learning for Formulations
• Updated Tutorial: Update tutorials for switch to RDKit (affects multiple tutorials)