Prediction of protein H/D exchange dynamics using structure based model simulations

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

San Javier, Tucumán

Congreso; Biophysical Society of Argentina 41th Annual Meeting; 2012

Sociedad Argentina de Biofísica

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. Hydrogen exchange is one of the experimental techniques that provide this type of information. The development of methods to quantitatively compare this experimental parameter with simulations is important. We recently developed a method for the analysis of the local stability of proteins and the prediction of native HX protection factors in EX2 conditions using coarse grained structure based model simulations, which allow a fast and thorough analysis of both local and global unfolding transitions1. 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 our molecular dynamics based approach to study the exchange dynamics of ubiquitin in the EX1 limit, providing information about the rate of the opening reactions. A variety of simulation models with additive as well as non additive contact potentials were evaluated for their agreement with experiments.