FTMAP

FTMAP maps binding hot spots on protein surfaces by sampling small organic molecule probes to identify low-energy binding regions relevant to drug design.

Key Features:

• Global surface sampling: Samples the entire protein surface with small organic molecule probes to determine favorable binding positions.
• Clustering and energy ranking: Clusters probe conformations and ranks clusters based on average energy to identify low-energy sites.
• Hot spot identification: Identifies regions where multiple probe clusters converge as predicted binding hot spots.
• Custom probe support: Accepts any user-supplied small molecule as an additional probe for analysis.
• Pose prediction: Provides predicted bound poses and representative structures of nearby low-energy clusters for additional probes.
• Binding likelihood assessment: Assesses the likelihood of user probes binding within identified hot spot regions.
• Experimental correlation: Produces predictions that align with experimental mapping methods such as X-ray crystallography and NMR.

Scientific Applications:

• Drug discovery: Prioritizes binding hot spots to guide fragment-based and structure-based drug discovery.
• Structural biology: Complements experimental mapping by highlighting protein-ligand interaction hotspots observed with X-ray crystallography and NMR.
• Ligand design: Aids design of larger ligands by revealing adjacent low-energy clusters suitable for fragment linking or growing.
• Fragment screening simulation: Simulates screening of small organic probes on protein surfaces to identify fragment binding motifs.
• Binding site characterization: Characterizes and ranks potential binding sites for lead optimization and downstream docking studies.

Methodology:

Globally sample the protein surface with small organic molecule probes, cluster probe conformations, rank clusters by average energy, identify consensus regions where multiple probe clusters converge, and process user-supplied small-molecule probes to return representative low-energy cluster poses.