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MPKaDB: A pKa Database for Exploring pH Dependence in Membrane Proteins

He, J.; Chen, Y.; Wu, J.; Cai, Z.; Jia, W.; Yue, Q.; Huang, Y.

2025-11-17 molecular biology
10.1101/2025.11.14.688495 bioRxiv
Show abstract

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 pKa 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 pKa 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 pKas from MPKaDB could be applied to explore the pH-dependent relationship between membrane protein structure and function. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/688495v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@f90726org.highwire.dtl.DTLVardef@1448ac2org.highwire.dtl.DTLVardef@f1e4f4org.highwire.dtl.DTLVardef@ee57dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

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