ProBiS-Dock

ProBiS-Dock performs flexible docking of small molecules and proteins using Protein Data Bank (PDB) structures to predict ligand–protein interactions while modeling conformational changes in both partners.

Key Features:

• Hybrid Multitemplate Homology Flexible Docking Algorithm: Combines homology modeling with multitemplate flexible docking to accommodate variable protein templates and model conformational changes.
• ProBiS-Score Functionality: Implements a two-component scoring function comprising a binding site-specific ProBiS-Score and a general statistical scoring term to evaluate docking poses.
• Rapid Docking Capability: Optimized for rapid docking of small molecules to proteins to support high-throughput virtual screening.
• Validation and Benchmarking: Validated against standard benchmarks and applied to identify new active ligands, including inhibitors of human indoleamine 2,3-dioxygenase 1 (IDO1).

Scientific Applications:

• Drug discovery: Enables rapid identification of novel active ligands by searching and comparing structural data from the Protein Data Bank (PDB) for compatible binding sites.
• IDO1 inhibitor discovery: Applied to discover inhibitors of human indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme involved in l-tryptophan metabolism via the kynurenine pathway with relevance to cancer therapy.

Methodology:

Compares protein binding sites from PDB structures with ligands explicitly incorporated, applies a hybrid multitemplate homology flexible docking algorithm to model conformational changes, and evaluates poses using the binding site-specific ProBiS-Score combined with a general statistical scoring function.