Very fast empirical prediction and rationalization of protein pKa values
Tóm tắt
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.
Từ khóa
Tài liệu tham khảo
Jeffrey GA, 1997, An introduction to hydrogen bonding
Sundd M, 2002, Investigation of electrostatics in ubiquitin by mutagenesis and NMR, Biophys J, 82, 299a
Garcia‐Moreno B, 1998, Solvent penetration may be responsible for the high dielectric constant inside a protein, Biophys J, 74, A132
Spencer DS, 1998, The pK(a) of buried ionizable groups in staph nuclease: an experimental measure of the dielectric constant of a protein interior, Biophys J, 74, A170
Jia ZC, 1993, The 2.0‐Angstrom resolution structure of Escherichia coli histidine‐containing phosphocarrier protein Hpr—a redetermination, J Biol Chem, 268, 22490, 10.1016/S0021-9258(18)41556-6
Ido E, 1991, Kinetic‐studies of human‐immunodeficiency‐virus type‐1 protease and its active‐site hydrogen‐bond mutant A28s, J Biol Chem, 266, 24359, 10.1016/S0021-9258(18)54237-X
Wada A, 1976, The alpha‐helix as an eletric macrodipole, Adv Biophys, 9, 1