Download Schrodinger Suites 2025-1 x64 Windows/Linux/macOS

Small Molecule Drug Discovery

Target Validation & Structure Enablement
Protein Preparation
– Improved peptide bond connectivity by better integration of sequence information in the Protein Preparation Workflow (PPW)
Protein X-Ray Refinement
– Phenix/OPLS can now run from CIF files containing reflections
Cryo-EM Model Refinement
– Improved support of macrocycles in GlideEM/GlideXtal

Binding Site & Structure Analysis
Binding Site Characterization
– Rationalize kinase selectivity challenges using the Kinase Conservation Analysis Interface that combines sequence and complex structural information: Identify promising selectivity handle residues to modulate ligand kinase selectivity that can be tested with FEP+ Residue Scan
Desmond Molecular Dynamics
– Optimize the unbinding kinetics of protein-ligand complexes using dissolution rate predictions based on unbinding pathways identified by enhanced sampling methods
Mixed Solvent MD (MxMD)
– Identify potential binding sites and assess drugability of competitive and allosteric binding sites with the full release of a Mixed Solvent Molecular Dynamics Interface to setup and analyze MxMD simulations

Hit Identification & Virtual Screening
Active Learning Applications
– Improved diversity of top scoring ligands in Active Learning ABFEP by using 3D features extracted from Glide poses in ML model building
– Researchers can now specify different batch sizes and selection rules to exploit or explore for each iteration in Active Learning simulations

Lead Optimization
Protein FEP
– View trajectories and structural output from FEP+ Residue Scans in the FEP+ interface
– Rationalize key interactions in ligand binding using per-contact residue interaction energy analysis which is new for ABFEP
– Easily identify disconnected sub-maps in a busy FEP map
Spectroscopy
– More accurate NMR spectra predictions by identifying magnetically inequivalent nuclei
Macrocycles
– Automatically enumerate and cyclize peptide sequences from FASTA files with the new cyclize_peptide.py script
– Ring template generation for Glide macrocycle docking with bespoke parameters is now automated by the macrocycle_template_gen.py script
– An updated macrocycle_sample.py script with greater control of sampling options and a new receptor-aware macrocycle sampling algorithm that includes surrounding receptor atoms to restrict conformational search space
. Updated macrocycle_sample.py script replaces macro_sample.py
– Improved handling of ring nitrogen atom substituents during ring template conformation generation
– tug_align.py now supports 2D ligand files as inputs
– tug_align.py exposes several new command-line options that allow finer control of the alignment convergence criteria which are useful in reducing convergence times for large molecules such as cyclic peptides

Medical Chemistry Design
Ligand Designer
– Enable user-specificed or automatically generated ligand protonation and tautomeric states from the 2D/3D editing workflow for MCS Docking

Biologics Drug Discovery

– Completely rewritten MMGBSA Residue Scanning backend that is more reliable and has improved support for a wider variety of non-standard amino acids and mutation of DNA/RNA
– New high-throughput, machine learning-based antibody and nanobody structure prediction with ImmuneBuilder. With throughput of about one minute per structure, it is suitable for batch modeling of thousands of structures
– Automatically identify and annotate for visualization TCR alpha and beta chains from a FASTA file (commandline run_tcr_modeling.py)
– Updated N-glycosylation PROSITE pattern that is less restrictive

Materials Science

GUI for Quantum ESPRESSO
Product: Quantum ESPRESSO (QE) Interface
– Workflow solution to calculate the defect energy
– Workflow action menu (WAM) for output from periodic DFT convergence test
– Support for setting total magnetization/charge for each structure
– Support for computing thermodynamic properties via dynmat.x (command line)
– Support for stopping an NEB calculation and returning intermediate structures
Materials Informatics
Product: MS Informatics
– Formulation ML: Option to control advanced settings
– Machine Learning Property: Skip structures outside the model scope
– Machine Learning Property: Prediction of singlet (S0) to triplet (T1) energy
– Machine Learning Property: Prediction of hole / electron reorganization energy
– Machine Learning Property: Prediction of orbital (HOMO / LUMO) energy
– Machine Learning Property: Updates to existing models
Coarse-Grained (CG) Molecular Dynamics
Product: MS CG
– Automated CG Mapping: Mapping MARTINI for speciality chemicals / polymers
– CG FF Builder: Support for exporting atomistic reference data
Dielectric properties
Product: MS Dielectric
– Complex Permittivity: Linear fitting parameter retained during exponential fitting
Reactivity
Product: MS Reactivity
– Nanoreactor: Control over thermostat bath temperature
– Nanoreactor: Support for parallelization of xTB dynamics simulations
– Reaction Workflow: Support for the use of the xTB Hessian for transition states
– Reaction Workflow: Use of input conformers when conformation search fails
– Reaction Workflow: Improved SCF convergence for energy calculations
Microkinetics
Product: MS Microkinetics
– Microkinetic Modeling: Improved speed/scalability by up to 2 orders of magnitude
– Microkinetic Modeling: Improved model for multiple catalysts / catalyst site types
– Microkinetic Modeling: Improved data visualization in the viewer
– Microkinetic Modeling: Job name shown in the viewer
Reactive Interface Simulator
Product: MS RIS
– Solid Electrolyte Interphase: Improved subjob queuing coordination
– Solid Electrolyte Interphase: Support for constant pressure (NpT) simulations (command-line)
MS Maestro Builders and Tools
– GUI panel to digitally design, manage, and visualize OLED devices
– Single Complex: Improved UI for better usability
– Solvate System: Support for generating multiple configurations by random seeds
Classical Mechanics
– Workflow solution to compute thin plane shear friction
– Barrier Potential for MD: Support for reading barrier information from entry
– Evaporation: Option to plot total number of molecules removed from the system
– Evaporation: Information tied to barriers (when applied) logged in the output
– Polymer Crosslink: Improved speed by efficient checking for ring spears
– Trajectory Density Analysis: Option to display multiple density depths
– Trajectory Density Analysis: Export option for 2D heat-map plot
Quantum Mechanics
– Workflow solution to plot phase diagrams based on energy
– Workflow solution to compute and analyze computational ellipsometry data
– QM Convergence Monitor: Easy access to the structure from the last step

Education Content

Life Science
– New tutorial: Refining crystallographic protein-ligand structures using GlideXtal and Phenix/OPLS
Materials Science
– New tutorial: Automated Martini Fitting for Coarse-Grained Simulations
– New tutorial: Thin Shear
– New tutorial: Defect Energy Calculation
– New tutorial: Optoelectronics Device Designer
– New tutorial: Computational Ellipsometry
– New tutorial: Phase Diagrams
– New tutorial: Ab initio Molecular Dynamics Simulations of Li-ion Diffusion in Solid State Electrolytes
– Updated tutorial: Microkinetic Modeling
– Updated tutorial: Organometallic Complexes

LiveDesign

What’s upcoming in 2025-1
– Extended support for biologics drug discovery: Synchronous selection between Sequence Viewer and 3D Visualizer, support for biologic entities in models which expect atomistic representation, and enhancements for handling non-canonical monomers throughout the application
– Data import performance improvements: Faster small molecule file import and large enumeration result import
– Enhanced formula capabilities: Support multiple value inputs to a formula and align multiple value outputs from a formula by experiment, lot, or pose

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

• – Create customizable histograms from numerical data that are automatically synchronized with selection or filtering in other charts, the Project Table, or Workspace
• – Improved support for T-Cell Receptors with display of their annotations in the Structure Hierarchy
• Force Field
• – Full release of the OPLS5 polarizable force field for organic atoms for improved FEP+ and Desmond model accuracy

• – Ability to use a single generic protocol regardless of model input columns
• – LiveDesign connection node can take credentials from the session rather than storing them in the workflow
• – Date type columns are supported as LiveDesign model input

• – Enable compact mode for sites with volume larger than a cutoff
• – New RNA mode for improved performance of SiteScore for RNA

• – New Unbinding Kinetics workflow to gain insights into drug-target residence time and optimize in vivo efficacy, safety profiles, and ADMET (beta)
• – Analyze halogen bonds in SID Panel
• – View local strain energy in “Torsion” tab of SID Panel

• – Improved organization of output structures and data in prjzip file

• – Streamline visualization of hits in the Hit Analyzer by outputting VSDB per docking run by default
• – Streamlined generation of WScore models with new WScore Quick Model Generation panel (beta)

• – Filter chemotypes by SMARTS in Hit Analyzer Panel

• – Improved management of pKa/tautomer/conformer ensembles on ABFEP systems with Groups tab
• – Core-SMARTS selection no longer requires selecting explicit hydrogen atoms
• – Improved user interface allows more intuitive column sorting
• – Export to LiveDesign now includes additional fields
• – Edge analysis now includes halogen protein-ligand interactions
• – Guided access to open FEP+ Panel for analysis upon calculation completion via Workflow Action Menus (WAM) in Maestro

• – New lambda dynamics (λD) enhanced protein residue mutation FEP+ for identifying high quality protein variants (beta)
• – Expanded OPLS5 support for “Protein FEP” and “Protein FEP for Ligand Selectivity” panels

• – Expanded OPLS5 support for Solubility FEP simulations

• – Gain up to 35% speedup in calculations due to changed defaults in the FEP Protocol Builder panel

• – Perform DNA/RNA nucleobase mutations using residue scanning on command line via mut-pred.py
• – Analyze DNA/RNA interactions with proteins in the Protein Interaction Analysis panel
• – Search the non-standard residues library and find the closest matching natural amino acid analog
• – Automatically annotate and number T Cell Receptor (TCR) structures using IMGT or AHo schemes
• – Use pose-viewer files as input for Protein Interaction Analysis

• GUI for Quantum ESPRESSO
• Product: Quantum ESPRESSO (QE) Interface
• – Check for the number of irreducible k-points from the panel
• – Upgrade to Quantum ESPRESSO 7.3.1
• – Quicker assessment of electric field for faster phonon calculations
• – Force and stress information reported in the project table
• – Option for more diagonalization algorithms for GIPAW steps (command line)
• – Option to set separate driver and subjob hosts for NEB calculations
• – Solid State NMR Viewer: Improved UI for selecting elements

• – Diffusion: Support for non-orthorhombic systems as input

• Product: MS Informatics
• – Formulation ML: Option to use Machine Learning Property predictions as descriptors
• – Formulation ML: Option to use DeepAutoQSAR predictions as descriptors
• – Machine Learning Property: Updates to existing models
• – Machine Learning Property: Prediction of S1-T1 energy gap
• – Machine Learning Property: Prediction of aqueous solubility
• – Machine Learning Property: Output entries separated for each solvent

• – Coarse-Grained Force Field Builder: Automated mapping for dissipative particle dynamics (DPD)
• – Coarse-Grained Force Field Builder: Visualization of CG mapping in the workspace

• – Nanoreactor: Frames from MD trajectory added to list of products
• – Nanoreactor: Support for multistate (e.g. singlet-triplet) reactions
• – Nanoreactor: Number of loaded structures reported in the viewer
• – Nanoreactor: Plot for reactants (red) shown with products (blue) in the viewer
• – Nanoreactor: Reactant structures to be included as standard output
• – Reaction Workflow: Support for AutoTS output as input

• – Microkinetic Modeling: Support for renaming of reactions and participating species
• – Microkinetic Modeling: Automatic population of molecular weight for gas/solute species
• – Microkinetic Modeling: Automatic assigning of collision factor based on reaction type

• – Solvate System: Option to neutralize systems with built-in counterions

• – Barrier Potential for MD: Support for NPT ensemble
• – Elastic Constants: Option to reset the viewer panel
• – Meta Workflows: Support for trajectory-based free volume analysis
• – Order Parameter: Option to compute acentric order parameter
• – Polymer Crosslink: Option to use a barrier potential
• – Polymer Chain Analysis: Support for molecules with less than 40 atoms

• – Adsorption Energy: Option to constrain atomic positions for systems with PBC
• – Optoelectronic Film Properties: Workflow solution encompassing transition dipole moment orientation and singlet excitation energy transfer (SEET) calculations

• – New Tutorial: Introduction to MD Trajectory Analysis with Desmond
• – New Tutorial: Re-scoring Docked Ligands with MM-GBSA
• – Updated Tutorial: Understanding and Visualizing Target Flexibility
• – Updated Tutorial: Approximating Protein Flexibility without Molecular Dynamics

• – New Tutorial: Singlet Excitation Energy Transfer
• – New Tutorial: FEP Solubility
• – New Tutorial: Genetic Optimization
• – New Tutorial: Adsorption of Panthenol on Skin with All-Atom Molecular Dynamics
• – Updated Tutorial: Applying Barrier Potentials for Molecular Dynamics Simulations
• – Updated Tutorial: Automated Dissipative Particle Dynamics (DPD) Parameterization
• – Updated Tutorial: Design of Asymmetric Catalysts with Automated Reaction Workflow
• – Updated Tutorial: Machine Learning Property Prediction
• – Updated Tutorial: Crosslinking Polymers

• 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

• 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)

• 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

• Improved usability for several Project Table dialogs including Change Property, Substructure Count, Add Property, Add Sequential Index Property, Add Standard Molecular Property, Redo Calculation, and Total Surface Area
• Improved usability of the Find Toolbar by adding a close button and “Search in Progress” indication

• Stabilized version of the KNIME generic LiveDesign protocols
• New node for pKa prediction using Epik 7
• Added support for AB-FEP files to FEP+ reader node

• Improved accuracy of ligand ionization/tautomeric state predictions in the Protein Preparation Workflow using ML-enabled Epik by default
• Ability to optionally provide sequence information via FASTA file when filling in missing loops

• Ability to export sequences and annotations to seqD file

• Added Radial Distribution Function (RDF) analyzer in Trajectory Plots

• Improved accuracy in empirical corrections for Macro-pKa from a new ML-based algorithm used by default

• Improved functionality of FEP+ Panel-managed trajectories can now be moved out of the FEP+ entry group, to retain it in the project table

• Mutation generation will now ignore water molecules for sidechain placement

• Ability to compute hydration free energies from Solubility FEP with useful blood brain barrier penetration correlation: Hydration-only mode is now available from Advanced Options of the Solubility FEP panel

• Employ different basis sets by atom in Jaguar Transition Search
• Predict and view NMR spectra based on DFT chemical shifts and spin-spin couplings
• Added support for analytic basis sets with high angular momenta including cc-pvXz and def2 basis sets up to QZ
• Added support for composite 3c-functionals: HF-3c, PBEh-3c, HSE-3c, B97-3c, r2SCAN-3c, and wB97X-3c

• Improved accuracy in antibody modeling with new curated antibody database that now excludes redundant and/or poor-quality PDB structures
• Option to export all 1000 unclustered raw poses from PIPER protein docking
• Report the % humanness of the Heavy and Light chain on the grafted model in Antibody humanization by CDR grafting
• Export aggregation profile images in png format
• Report detailsed patch characteristics in Protein Patch calculations
• Easily perform detailsed analysis of residue scanning results with new csv file containing mutant descriptions and energies

• Convergence monitor for the nudged elastic band (NEB) calculations
• Workflow for computing dielectric constant (command line)
• Support for parallel computation of Phonon calculations (command line)
• Option to display discrete frequencies from dynamical matrix for phonon DOS
• Support for phonon calculations with Hubbard U potentials for LDA+U
• Support for mean square displacement analysis over an existing AIMD trajectory

• DeepAutoQSAR: Access from the Task menu under Materials Informatics
• Formulation ML: Machine-learning-based property predictions using chemical formulations
• Machine Learning Property: Improved machine learning models
• MD Descriptors: Bond, angle, torsion, and vdW energies computed as descriptors
• MD Descriptors: Improved efficiency with the MD simulation protocol

• CG FF Builder: Implicit charge assessment by dielectric constant
• Automated DPD Mapping: Support for multiple ionization states (command line)
• Automated DPD Mapping: Support for pre-defined patterns for use in mapping (command line)
• Support for including CGFF file (*.json) information into other CGFF files

• Schrödinger Nanoreactor: Chemical reaction discovery and analysis module based on AIMD and semiempirical QM (xTB) methods
• Auto Reaction Workflow: Improved speed in calculating custom rates and Keq

• Workflow module for microkinetic modeling of chemical reaction rates

• Complex Enumeration: Support for the use of two ligand libraries as input
• Complex Enumeration: Option to specify the number of unique ligands
• Move Selected Atoms: Workspace tool to rotate/translate selected atoms

• Polymer Crosslink: Option to block formation of specific chemical structures
• Molecular Deposition: UI update with improved control of adsorbate setup and simulation protocols

• TST Rate: Jobs launched to queue

• New Tutorial: Microkinetic Modeling
• New Tutorial: Machine Learning for Formulations
• New Tutorial: Nanoreactor
• New Tutorial: Modeling Receptor Binding in an Olfactory Protein
• New Tutorial: Building a Coarse-Grained Skin Model using Martini Force Field
• Updated Tutorial: Activation Energies for Reactivity in Solids and on Surfaces
• Updated Tutorial: Molecular Deposition