ESSENTIAL DYNAMICS OF PROTEINS

Analysis of extended molecular dynamics (MD) simulations of lysozyme i n vacuo and in aqueous solution reveals that it is possible to separat e the configurational space into two subspaces: (1) an ''essential'' s ubspace containing only a few degrees of freedom in which anharmonic m otion occurs that comprises most of the positional fluctuations; and ( 2) the remaining space in which the motion has a narrow Gaussian distr ibution and which can be considered as ''physically constrained.'' If overall translation and rotation are eliminated, the two spaces can be constructed by a simple linear transformation in Cartesian coordinate space, which remains valid over several hundred picoseconds. The tran sformation follows from the covariance matrix of the positional deviat ions. The essential degrees of freedom seem to describe motions which are relevant for the function of the protein, while the physically con strained subspace merely describes irrelevant local fluctuations. The near-constraint behavior of the latter subspace allows the separation of equations of motion and promises the possibility of investigating i ndependently the essential space and performing dynamic simulations on ly in this reduced space. (C) 1993 Wiley-Liss, Inc.