MODEL-FREE METHODS OF ANALYZING DOMAIN MOTIONS IN PROTEINS FROM SIMULATION - A COMPARISON OF NORMAL-MODE ANALYSIS AND MOLECULAR-DYNAMICS SIMULATION OF LYSOZYME

Model-free methods are introduced to determine quantities pertaining t o protein domain motions from normal mode analyses and molecular dynam ics simulations, For the normal mode analysis, the methods are based o n the assumption that in low frequency modes, domain motions can be we ll approximated by modes of motion external to the domains, To analyze the molecular dynamics trajectory, a principal component analysis tai lored specifically to analyze interdomain motions is applied, A method based on the curl of the atomic displacements is described, which yie lds a sharp discrimination of domains, and which defines a unique inte rdomain screw-axis, Hinge axes are defined and classified as twist or closure axes depending on their direction, The methods have been teste d on lysozyme, A remarkable correspondence was found between the first normal mode axis and the first principal mode axis, with both axes pa ssing within 3 Angstrom of the alpha-carbon atoms of residues 2, 39, a nd 56 of human lysozyme, and near the interdomain helix, The axes of t he first modes are overwhelmingly closure axes, A lesser degree of cor respondence is found for the second modes, but in both cases they are more twist axes than closure axes, Both analyses reveal that the inter domain connections allow only these two degrees of freedom, one more t han provided by a pure mechanical hinge. (C) 1997 Wiley-Liss, Inc.