Improved pKa calculations through flexibility based sampling of a water-dominated interaction scheme.

ABSTRACT: Ionizable groups play critical roles in biological processes. Computation of pK(a)s is complicated by model approximations and multiple conformations. Calculated and experimental pK(a)s are compared for relatively inflexible active-site side chains, to develop an empirical model for hydration entropy changes upon charge burial. The modification is found to be generally small, but large for cysteine, consistent with small molecule ionization data and with partial charge distributions in ionized and neutral forms. The hydration model predicts significant entropic contributions for ionizable residue burial, demonstrated for components in the pyruvate dehydrogenase complex. Conformational relaxation in a pH-titration is estimated with a mean-field assessment of maximal side chain solvent acces

SUBMITTER: Warwicker J 

PROVIDER: S-EPMC2286538 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature