Very fast empirical prediction and rationalization of protein pK a values

Hui Li, Andrew D. Robertson, Jan H. Jensen

Research output: Contribution to journalArticlepeer-review

1745 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)704-721
Number of pages18
JournalProteins: Structure, Function and Genetics
Issue number4
StatePublished - Dec 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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