Uncovering pH-dependent transient states of proteins with buried ionizable residues.

ABSTRACT: The role of pH in regulating biological activity is ubiquitous, and understanding pH-mediated activity has traditionally relied on analyzing static biomolecular structures of highly populated ground states solved near physiological pH. However, recent advances have shown the increasing importance of transiently populated states, the characterization of which is extremely challenging but made plausible with the development of techniques such as relaxation dispersion NMR spectroscopy. To unlock the pH dependence of these transient states with atomistic-level details, we applied the recently developed explicit solvent constant pH molecular dynamics (CPHMD(MSλD)) framework to a series of staphylococcal nuclease (SNase) mutants with buried ionizable residues and probed their dynamics in differe

SUBMITTER: Goh GB 

PROVIDER: S-EPMC4227812 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature