A kinetic model for the internal motions of proteins: Diffusion between multiple harmonic wells

The dynamics of collective protein motions derived from Molecular Dynamics simulations have been studied for two small model proteins: initiation fact or I and the B1 domain of Protein G. First, we compared the structural fluc tuations, obtained by local harmonic approximations in different energy min ima, with the ones revealed by large scale molecular dynamics (MD) simulati ons. It was found that a limited set of harmonic wells can be used to appro ximate the configurational fluctuations of these proteins, although any sin gle harmonic approximation cannot properly describe their dynamics. Subsequently, the kinetics of the main (essential) collective protein motio ns were characterized. A dual-diffusion behavior was observed in which a fa st type of diffusion switches to a much slower type in a typical time of ab out 1-3 ps, From these results, the large backbone conformational fluctuati ons of a protein may be considered as "hopping" between multiple harmonic w ells on a basically flat free energy surface. (C) 1999 Wiley-Liss, Inc.