Normal mode analysis of human lysozyme : study of the relative motion of the two domains and characterization of the harmonic motion

A normal mode analysis of Human Lysozyme has been carried out at room temperature. Human Lysozyme is an enzyme constituted of two domains separated by an active site cleft, the motion of which is thought to be relevant for the biological function. This motion has been described as a hinge bending motion. McCammon et al.1 have determined the characteristics of the hinge bending motion but they assumed a prior knowledge of the hinge axis. In this work we propose a method which is free from this assumption and determines the hinge axis and root-mean-square (r.m.s.) rotation angle which give the best agreement with the pattern of changes in all the distances between nonhydrogen atoms in the two domains, obtained by the normal mode analysis. The hinge axis we found is notably different from the one previously determined and goes, roughly, through the Cα 55 and Cα 76, i.e., it is located at the base of the p sheet of the second domain. The r.m.s. value for the rotation angle is also twice as large as the previous one: 3.37 degrees. It is shown that this hinge bending motion provides a fairly good approximation of the dynamics of Human Lysozyme and that the normal mode with the lowest frequency has a dominating contribution to this hinge bending motion