David E. Shaw,Paul Maragakis,Kresten Lindorff‐Larsen,Stefano Piana,Ron O. Dror,Michael P. Eastwood,Joseph A. Bank,John Jumper,John K. Salmon,Yibing Shan,Willy Wriggers
出处
期刊:Science [American Association for the Advancement of Science (AAAS)] 日期:2010-10-14卷期号:330 (6002): 341-346被引量:1747
Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.