Cosolvent Analysis Toolkit (CAT)

Cosolvent Analysis Toolkit (CAT) analyzes cosolvent molecular dynamics (MD) trajectories to identify and characterize protein binding sites and to rank interactions relevant for small-molecule ligand targeting.

Key Features:

• Automated cosolvent MD analysis: Performs automated analysis of cosolvent molecular dynamics (MD) trajectories to detect ligand–binding events and protein hotspots.
• Hybrid empirical force field scoring function: Uses a hybrid empirical force field scoring function to rank dynamic interactions between macromolecular targets and cosolvent molecules.
• Allosteric and cryptic site identification: Identifies and prioritizes allosteric and cryptic binding sites alongside orthosteric sites for downstream ligand design.
• Addresses pocket-volume limitations: Mitigates limitations of traditional pocket-volume–based cosolvent MD analyses by using dynamic interaction scoring to reduce manual bias.
• Compatibility with molecular graphics software: Produces outputs compatible with UCSF Chimera and VMD for visualization and further structural analysis.
• Benchmark validation: Validated on three protein targets using five chemically distinct cosolvent molecules, successfully recovering known binding sites.

Scientific Applications:

• Hotspot discovery: Detection and ranking of protein "hotspots" for fragment or small-molecule ligand placement.
• Allosteric site mapping: Identification of allosteric and cryptic sites for target modulation beyond orthosteric pockets.
• Druggability assessment: Prioritization of protein regions to expand the druggable proteome and guide medicinal chemistry efforts.
• Comparative analysis: Evaluation of cosolvent effects across chemically distinct probe molecules to inform probe selection and interpretation.

Methodology:

Automated analysis of cosolvent MD trajectories using a hybrid empirical force field scoring function to rank dynamic interactions between macromolecular targets and cosolvent molecules, with validation on three protein targets using five chemically distinct cosolvent molecules.