Predicting extreme pKa shifts in staphylococcal nuclease mutants with constant pH molecular dynamics.

ABSTRACT: Accurate computational methods of determining protein and nucleic acid pK(a) values are vital to understanding pH-dependent processes in biological systems. In this article, we use the recently developed method constant pH molecular dynamics (CPHMD) to explore the calculation of highly perturbed pK(a) values in variants of staphylococcal nuclease (SNase). Simulations were performed using the replica exchange (REX) protocol for improved conformational sampling with eight temperature windows, and yielded converged proton populations in a total sampling time of 4 ns. Our REX-CPHMD simulations resulted in calculated pK(a) values with an average unsigned error (AUE) of 0.75 pK units for the acidic residues in Δ + PHS, a hyperstable variant of SNase. For highly pK(a)-perturbed SNase mutants with

SUBMITTER: Arthur EJ 

PROVIDER: S-EPMC3213318 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature