ProBiS-CHARMMing

ProBiS-CHARMMing predicts and refines protein–ligand complexes by combining ProBiS binding-site similarity searches with CHARMMing CHARMM force-field optimization to generate ligand-bound models from apo protein structures.

Key Features:

• Integration of ProBiS and CHARMMing: Combines ProBiS binding-site comparison and ligand transposition with CHARMMing refinement using the CHARMM force field.
• Generation of ligand-bound models from apo structures: Transposes ligands from structurally similar binding sites to produce candidate holo models when experimental holo structures are absent.
• Binding-site similarity search (ProBiS): Compares the query protein surface against a non-redundant database of known structures to identify similar binding sites and propose observed ligands.
• Complex optimization (CHARMMing): Refines predicted protein–ligand complexes with the CHARMM force field to improve stereochemistry and interaction geometry.
• Interaction energy estimation: Computes interaction energies between predicted ligands and the query protein to assess complex stability and plausibility.

Scientific Applications:

• Drug design: Prioritizes compounds predicted to interact favorably with target proteins via structure-based modeling.
• Molecular docking studies: Provides refined starting conformations that better approximate ligand-bound states for docking workflows.
• Structural biology research: Improves models of protein–ligand interactions to support functional and dynamical interpretation.

Methodology:

Ligand prediction via ProBiS: compare the query protein surface to a non-redundant database of known structures to identify similar binding sites and transpose observed ligands onto the query protein. Optimization and energy calculation via CHARMMing: refine the resulting complexes using the CHARMM force field and compute interaction energies to evaluate stability of the predicted protein–ligand interactions.