Schrodinger Suites 2025-1

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