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Very fast empirical prediction and rationalization of protein pKa values

Authors

  • Hui Li,

    1. Department of Chemistry and Center for Biocatalysis and Bioprocessing, The University of Iowa, Iowa City, Iowa
    Current affiliation:
    1. Department of Chemistry, Iowa State University, Ames, Iowa 50011
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  • Andrew D. Robertson,

    1. Department of Biochemistry, The University of Iowa, Iowa City, Iowa
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  • Jan H. Jensen

    Corresponding author
    1. Department of Chemistry and Center for Biocatalysis and Bioprocessing, The University of Iowa, Iowa City, Iowa
    • Department of Chemistry and Center for Biocatalysis and Bioprocessing, The University of Iowa, Iowa City, Iowa 52242
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Abstract

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.

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