Analysis of Native H/D exchange dynamics using structure based model simulations

CRAIG PO; LATZER J; WEINKAM P; HOFFMAN, RMB; KOMIVES EA; WOLYNES P

San Diego, California, USA.

Congreso; Biophysical Society 56th Annual Meeting,; 2012

Craig PO, Lätzer J, Weinkam P, Hoffman R, Komives E, Wolynes P.

The analysis of kinetic and thermodynamic data measured at single residue level, and the perturbation produced by mutagenesis or denaturant agents, may be useful for tuning simulation parameters, and provide a precise description of proteins structural dynamics. Phi value and hydrogen exchange are some of the experimental techniques that provide this type of information at different depths on the folding funnel. The development of methods to quantitatively compare these experimental parameters with simulation is required. We recently developed a method for the quantitative analysis of native HX protection factors in EX2 conditions using coarse grain structure based model simulations, which allow a fast and thorough analysis of both local and global unfolding transitions. This analysis applied to ubiquitin, chymotrypsin inhibitor, and Staphylococcal nuclease, allowed us to establish optimum structural definitions for the exchange competent and incompetent states. In this work, we extend the method to study the exchange dynamics of ubiquitin in the EX1 limit, which provides information about the rate of the opening reactions. A variety of simulation models with homogeneous, heterogeneous, additive as well as non additive contact potentials were evaluated for their agreement with experiment.