CHAOS IN PROTEIN DYNAMICS

MD simulations, currently the most detailed description of the dynamic evolution of proteins, are based on the repeated solution of a set of differential equations implementing Newton's second law. Many such sy stems are known to exhibit chaotic behavior, i.e., very small changes in initial conditions are amplified exponentially and lead to vastly d ifferent, inherently unpredictable behavior, We have investigated the response of a protein fragment in an explicit solvent environment to v ery small perturbations of the atomic positions (10(-3)-10(-9) Angstro m). Independent of the starting conformation (native-like, compact, ex tended), perturbed dynamics trajectories deviated rapidly, leading to conformations that differ by approximately 1 Angstrom RMSD within 1-2 ps, Furthermore, introducing the perturbation more than 1-2 ps before a significant conformational transition leads to a loss of the transit ion in the perturbed trajectories, We present evidence that the observ ed chaotic behavior reflects physical properties of the system rather than numerical instabilities of the calculation and discuss the implic ations for models of protein folding and the use of MD as a tool to an alyze protein folding pathways. (C) 1997 Wiley-Liss, Inc.