Very fast empirical prediction and rationalization of protein pKa values
Article first published online: 17 OCT 2005
Copyright © 2005 Wiley-Liss, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 61, Issue 4, pages 704–721, 1 December 2005
How to Cite
Li, H., Robertson, A. D. and Jensen, J. H. (2005), Very fast empirical prediction and rationalization of protein pKa values. Proteins, 61: 704–721. doi: 10.1002/prot.20660
- Issue published online: 17 NOV 2005
- Article first published online: 17 OCT 2005
- Manuscript Accepted: 2 JUN 2005
- Manuscript Revised: 12 MAY 2005
- Manuscript Received: 11 MAR 2005
- National Science Foundation. Grant Number: MCB 0209941
- National Institutes of Health. Grant Number: GM 46869
A very fast empirical method is presented for structure-based protein pKa prediction and rationalization. The desolvation effects and intra-protein interactions, which cause variations in pKa values of protein ionizable groups, are empirically related to the positions and chemical nature of the groups proximate to the pKa sites. A computer program is written to automatically predict pKa values based on these empirical relationships within a couple of seconds. Unusual pKa values at buried active sites, which are among the most interesting protein pKa values, are predicted very well with the empirical method. A test on 233 carboxyl, 12 cysteine, 45 histidine, and 24 lysine pKa values in various proteins shows a root-mean-square deviation (RMSD) of 0.89 from experimental values. Removal of the 29 pKa values that are upper or lower limits results in an RMSD = 0.79 for the remaining 285 pKa values. Proteins 2005. © 2005 Wiley-Liss, Inc.