grand

grand performs grand canonical Monte Carlo sampling of water molecules within OpenMM to enable insertion and deletion of waters at a fixed chemical potential for studying hydration in biomolecular systems such as occluded protein-ligand binding sites.

Key Features:

• Grand Canonical Monte Carlo (GCMC) Sampling: Conducts GCMC simulations that allow insertion and deletion of water molecules, reducing equilibration times relative to conventional molecular dynamics.
• Integration with OpenMM: Implements GCMC within the OpenMM simulation engine to combine molecular dynamics and grand canonical sampling in a single computational framework.
• Enhanced Sampling in Complex Environments: Enables sampling of water in buried or occluded binding sites by inserting or deleting waters based on a fixed chemical potential, improving characterization of hydration in challenging environments.
• Validation and Application: Reproduces bulk water density observed in constant-pressure simulations and has identified three buried crystallographic water sites in bovine pancreatic trypsin inhibitor that are poorly sampled by conventional molecular dynamics.

Scientific Applications:

• Biomolecular hydration analysis: Study how water molecules influence structural and functional properties of biomolecular systems.
• Drug discovery and ligand design: Analyze water networks at binding sites to inform design and optimization of therapeutic agents.
• Protein–ligand interaction modeling: Elucidate mechanisms of protein-ligand interactions and improve predictive modeling of binding environments.

Methodology:

Implements grand canonical Monte Carlo (GCMC) within OpenMM to insert and delete water molecules at a fixed chemical potential; validated by comparison to constant-pressure bulk water density and by identifying buried crystallographic waters in bovine pancreatic trypsin inhibitor.