title: Very fast empirical prediction and rationalization of protein pKa values.
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.
authors.affiliation: Department of Chemistry, Center for Biocatalysis and Bioprocessing, The University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Robertson
authors.forename: Jan H
authors.initials: JH
authors.lastname: Jensen
mesh_terms: D000596:Amino Acids / Q000032:analysis; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012984:Software
chemical_list: D000596:Amino Acids; D011506:Proteins