Studying the switching of proteins involved in signal transduction with path-based molecular dynamics simulations

PHYS 12

Albert C Pan, acpan@uchicago.edu and Benoît Roux, roux@uchicago.edu. Institute for Molecular Pediatric Sciences, The University of Chicago, Gordon Center for Integrative Sciences, 929 East 57th Street, Chicago, IL 60637
Conformational changes of proteins lie at the heart of fundamental biological processes. In particular, relaying information in biochemical signaling networks relies on the allosteric regulation of protein conformational dynamics. We have developed and applied novel path-based molecular dynamics computer simulation methods to probe the conformational switching of nitrogen regulatory protein C, an important allosterically regulated protein involved in bacterial two-component signal transduction networks. Our path-based method is a dynamic extension of free energy perturbation and minimum free energy path techniques, allowing an accurate and efficient determination of the rates and mechanisms of biomolecular conformational changes.