Very fast empirical prediction and rationalization of protein pK a values

• Published in: Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2005-12, Vol.61 (4), p.704-721
• Main Authors: Li, Hui, Robertson, Andrew D., Jensen, Jan H.
• Format: Article
• Language: English
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.20660

A very fast empirical method is presented for structure‐based protein pK a prediction and rationalization. The desolvation effects and intra‐protein interactions, which cause variations in pK a values of protein ionizable groups, are empirically related to the positions and chemical nature of the groups proximate to the pK a sites. A computer program is written to automatically predict pK a values based on these empirical relationships within a couple of seconds. Unusual pK a values at buried active sites, which are among the most interesting protein pK a values, are predicted very well with the empirical method. A test on 233 carboxyl, 12 cysteine, 45 histidine, and 24 lysine pK a values in various proteins shows a root‐mean‐square deviation (RMSD) of 0.89 from experimental values. Removal of the 29 pK a values that are upper or lower limits results in an RMSD = 0.79 for the remaining 285 pK a values. Proteins 2005. © 2005 Wiley‐Liss, Inc.