PKa of residue 66 in Staphylococal nuclease. I. Insights from QM/MM simulations with conventional sampling.

ABSTRACT: A combined quantum mechanical/molecular mechanical (QM/MM) potential function is used in a thermodynamic integration approach to calculate the pK(a) of residue 66 in two mutants (V66E, V66D) of Staphylococal nuclease relative to solution. Despite the similarity in chemical nature and experimentally measured pK(a) of the two buried titritable residues, the behaviors of the two mutants and the computed pK(a) values vary greatly in the simulations. For Glu66, the side chain is consistently observed to spontaneously flip out from the protein interior during titration, and the overall protein structure remains stable throughout the simulations. The computed pK(a) shifts using conventional sampling techniques with multiple nanoseconds per lambda window (Set A and B) are generally close to the ex

SUBMITTER: Ghosh N 

PROVIDER: S-EPMC2562727 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature