The Short-Time Dynamics of Proteins Near Native State Conditions Signal to Robust Mechanisms Accessible at Long Times

Abstract

A number of recent computational studies have indicated that a robust pattern of motions is encoded by the particular architecture of a protein. These patterns have been shown to be of relevance to functional motions that occur on the much slower time scale of microseconds or longer. In addition, experimental data derived from NMR relaxation and other motion-containing NMR parameters as well as computational data from MD simulations indicate that the relative movements of residues at short times exhibit discernable correlations with those observed at long times. This intriguing issue was explored in the present work by conducting systematic molecular dynamics simulations of various durations, varying in the range 1 ns ≤ ttot ≤ 0.4 μs. While the observed amplitudes of motions are generally confined to 1 A in short simulations with a general increase to 2-3 A in the long ones, strikingly, the residue displacement distributions (away from equilibrium positions) exhibit comparable patterns. Careful examination of the relationship between the size of observed motion and the duration of simulations revealed a stretched exponential dependence of the the form y μ x0.26, with x as representing the ratio of simulation lengths and y the ratio of the motional amplitudes, consistent with the observations made by Scheraga and coworkers.11. Senet P, Maisuradze GG, Foulie C, Delarue P, Scheraga HA. How main-chains of proteins explore the free-energy landscape in native states. Proc. Natl. Acad. Sci. U. S. A (2008) 105: 19708-19713.