MPKaDB: A p K _a Database for Exploring pH Dependence in Membrane Proteins

The biological activities of many membrane proteins are pH-regulated, yet mapping their pH dependence experimentally is slow and expensive. In this work, we present MPKaDB ( http://computbiophys.com/DeepKa/mpkadb ), a comprehensive p K _a database for membrane proteins that instantly decode the protonation states of ionizable residues under a specified pH. Leveraging MPKaDB, we performed pH-coupled electrostatic characterization of trans-membrane proteins. To facilitate use, a user-friendly search engine was developed to retrieve a protein of interest and returns its p K _a values, isoelectric points of both cytoplasmic and extra-cytoplasmic faces, and an automated screening of active-site residues. In the end, two case studies were proposed to demonstrate how p K _a ’s from MPKaDB could be applied to explore the pH-dependent relationship between membrane protein structure and function.