THEORETICAL-ANALYSIS OF THE MULTICOPY SAMPLING METHOD IN MOLECULAR MODELING

Langevin Monte Carlo dynamics and equilibrium properties of the multic opy sampling approximation in the modeling of ligand-protein complexes are studied. A perturbation form is derived based on the normal mode analysis, and can be used as a quantitative means to estimate the appr oximation prior to running a multicopy simulation. The multicopy dynam ics is shown to induce an average dynamics of the protein and all the ligand copies, resulting in a well-defined equilibrium with uniform te mperature. The induced average dynamics and the equilibrium represent the desired physics of the multicopy approximation, and are extended t o include heterogeneous ligand copies. Such an extension presents a na tural way to incorporate biologically important information on evoluti on into energy-based molecular modeling of homologous proteins.