Monte Carlo study on local and small-amplitude conformational fluctuation in hen egg white lysozyme

Local and small-amplitude conformational fluctuations in hen egg white lysozyme around its native conformation were studied by the Monte Carlo simulation with conformational energy calculation. In order to carry out such a simulation in a shorter computation time, the following method was devised: at each step of the simulation a segment of consecutive four residues, say, i to i + 3, is chosen at random from N residues and then the small conformational change of the segment is performed so that the conformations of the two blocks of residues 1 to i - 1 and i + 4 to N as well as the mutual location of the two blocks are not changed. In this simulation it was found that calculated atomic displacements and fluctuations of dihedral angles well reflect the characteristics of local conformations, for example, stiffness of regular secondary structures and flexibility of non-regular structures, especially of the regions around the lips of the active-site cleft and of the region that undergoes conformational change on ligand binding to the active site. The flexibility of these regions is probably necessary for the reaction of the active site to the ligand. A close correlation between the solvent accessibility of the side chain of each residue and its flexibility was also observed. Furthermore, it was shown that the results obtained in this study are in a good agreement with the same properties observed in analyzing temperature factors derived from refinement of X-ray data of the protein.