CAPIM: Catalytic activity and site prediction and analysis tool in multimer proteins

Area of Science:

• Biochemistry and Structural Biology
• Computational Biology and Bioinformatics
• Enzymology

Background:

• Enzymes are crucial biological catalysts, but many proteins remain functionally uncharacterized.
• Existing computational tools often address enzymatic activity or active site detection separately, leaving a gap in residue-level functional annotation.
• Understanding enzyme function is vital for various biological processes and applications.

Purpose of the Study:

• To bridge the gap between residue-level annotation and functional characterization of enzymes.
• To introduce CAPIM (Catalytic Activity and Site Prediction and Analysis Tool In Multimer Proteins), an integrative computational pipeline.
• To provide a unified framework for predicting enzymatic activity, identifying catalytic sites, and validating function through docking.

Main Methods:

• CAPIM integrates P2Rank for binding pocket prediction, GASS for catalytic residue identification and EC number annotation, and AutoDock Vina for enzyme-substrate docking.
• The pipeline merges predictions to create residue-level activity profiles within identified pockets.
• It supports multi-chain protein complexes, including quaternary and polymeric structures.

Main Results:

• CAPIM successfully predicts binding pockets, identifies catalytic residues, and annotates enzymatic activities.
• Functional validation is achieved through substrate docking simulations for user-defined ligands.
• Case studies demonstrate CAPIM's utility on both characterized enzymes and unannotated multi-chain protein targets.

Conclusions:

• CAPIM offers a comprehensive computational resource for analyzing enzyme function at the residue level.
• The tool facilitates understanding of enzymes in complex protein structures, crucial for functions dependent on multimerization.
• CAPIM has broad applications in drug discovery and protein engineering, with availability as a standalone application and web service.