EFFICIENT SEARCH FOR ALL LOW-ENERGY CONFORMATIONS OF POLYPEPTIDES BY MONTE-CARLO METHODS

The Metropolis Monte Carlo method has been added to the program FANTOM for energy refinement of polypeptides and proteins using a Newton-Raphson minimizer in torsion angle space. With this extension, different strategies for global minimization of the semiempirical energy function ECEPP/2 by various temperature schedules and restriction of conformational space were tested for locating local minimum conformations with low energy of the pentapeptide Met-enkephalin. In total, 1881 conformations below - 10 kcal/mol were found. These conformations could be represented by 77 nonidentical conformations which were analysed for their pattern of hydrogen bonds, types of tight turn, pairwise root-mean-square-deviation (rmsd), Zimmermann codes and side chain conformations. All low energy conformations below - 10.4 kcal/mol show strong similarity to the global minimum conformation in the backbone structure.