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The determinants of carboxyl pK a values in turkey ovomucoid third domain
Author(s) -
Li Hui,
Robertson Andrew D.,
Jensen Jan H.
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20032
Subject(s) - hydrogen bond , chemistry , amide , solvent , serine protease , poisson–boltzmann equation , ab initio , computational chemistry , crystallography , protease , molecule , ion , organic chemistry , enzyme
Abstract A computational methodology for protein pK a predictions, based on ab initio quantum mechanical treatment of part of the protein and linear Poisson–Boltzmann equation treatment of the bulk solvent, is presented. The method is used to predict and interpret the pK a values of the five carboxyl residues (Asp7, Glu10, Glu19, Asp27, and Glu43) in the serine protease inhibitor turkey ovomucoid third domain. All the predicted pK a values are within 0.5 pH units of experiment, with a root‐mean‐square deviation of 0.31 pH units. We show that the decreased pK a values observed for some of the residues are primarily due to hydrogen bonds to the carboxyl oxygens. Hydrogen bonds involving amide protons are shown to be particularly important, and the effect of hydrogen bonding is shown to be nonadditive. Hydrophobic effects are also shown to be important in raising the pK a . Interactions with charged residues are shown to have relatively little effect on the carboxyl pK a values in this protein, in general agreement with experiment. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.