PROTEIN HINGE BENDING AS SEEN IN MOLECULAR-DYNAMICS SIMULATIONS OF NATIVE AND M6I MUTANT T4 LYSOZYMES

A dynamical model of interdomain ''hinge bending'' of T4 lysozyme in a queous solution has been developed on the basis of molecular dynamics (MD) simulation. The MD model study provides a description of the conf ormational reorganization expected to occur for the protein in aqueous solution as compared to the crystalline environment. Thr ee different 500 ps molecular dynamics simulations were calculated, each using a d istinctly different crystal conformation of T4 lysozyme as the startin g points of the MD simulations. Crystal structures of wild-type lysozy me and ''open'' and ''closed'' forms of M61 variant structures were an alyzed in this study. Large-scale, molecular-conformational rearrangem ents were observed in all three simulations, and the largest structura l change was found for the open form of the M61 allomorph. All three s imulated proteins had closed relative to the wild-type crystal structu re, and the closure of the ''jaws'' of the active site cleft occurred gradually over the time course of the trajectories. The time average M D structures, calculated over the final 50 ps of each trajectory, had all adapted to conformations more similar to each other than to their incipient crystal forms. Using a similar MD protocol on cytochrome P45 0BM-3 [M. D. Paulsen and R. L. Ornstein (1995) Proteins: Structure Fun ction and Genetics, Vol. 27, pp. 237-243] we have Sound that the oppos ite type of motion relative to the starting crystal structure, that is , the open form of the crystal structure, had opened to a greater degr ee relative to the incipient crystal structure form. Therefore we do n ot believe that either result is merely a simulation artifact, but rat her the protein dynamics are due to protein relaxation in the absence of crystal packing forces in the simulated solution environments. (C) 1997 John Wiley & Sons, Inc.