FTMove

FTMove maps binding hot spots across ensembles of protein structures to detect cryptic and allosteric binding sites and quantify their dependence on conformational variation.

Key Features:

• Multiple Structure Analysis: Analyzes ensembles of protein conformations from the Protein Data Bank (PDB) to identify binding hot spots across different structural states.
• Automated Mapping Process: Automatically retrieves relevant PDB structures and performs molecular probe mapping on each structure.
• Custom Structure Uploads: Accepts user-provided protein structures for mapping in addition to PDB-derived structures.
• Detailed Output Analysis: Reports consensus binding sites and individual mapping results per structure, including counts of probes per site to relate site strength to conformation, ligand presence, or mutations.
• Structural Clustering: Clusters structures based on their binding properties to reveal structural variation in binding characteristics.

Scientific Applications:

• Allosteric site identification: Applied to 22 proteins with known allosteric sites, FTMove identified orthosteric and allosteric binding sites in all but one case, with identified sites typically ranked among the top five.
• Structural biology and drug discovery: Detection of cryptic and allosteric sites and assessment of protein-ligand interaction variability across conformational ensembles for target evaluation and modulator design.

Methodology:

Automatically gather multiple PDB structures of the target, execute molecular probe mapping to identify binding hot spots on each structure, integrate individual mapping results into consensus binding sites, and cluster structures by binding properties.