SYSTEMATIC STEPSIZE VARIATION - EFFICIENT METHOD FOR SEARCHING CONFORMATIONAL SPACE OF POLYPEPTIDES

A new and efficient method for overcoming the multiple minima problem of polypeptides, the systematic stepsize variation (SSV) method, is pr esented. The SSV is based on the assumption that energy barriers can b e passed over by sufficiently large rotations about rotatable bonds: r andomly chosen dihedral angles are updated starting with a small steps ize (i.e., magnitude of rotation). A new structure is accepted only if it possesses a lower energy than the precedent one. Local minima are passed over by increasing the stepsize systematically. When no new str uctures are found any longer, the simulation is continued with the sta rting structure, but other trajectories will be followed due to the ra ndom order in updating the torsional angles. First, the method is test ed with Met-enkephalin, a peptide with a known global minimum structur e; in all runs the latter is found at least once. The global minimum c onformations obtained in the simulations show deviations of +/-0.0004 kcal/mol from the reference structure and, consequently, are perfectly superposable. For comparison, Metropolis Monte Carlo simulated anneal ing (MMC-SA) is performed. To estimate the efficiency of the algorithm depending on the complexity of the optimization problem, homopolymers of Ala and Gly of different lengths are simulated, with both the SSV and the MMC-SA method. The comparative simulations clearly reveal the higher efficiency of SSV compared with MMC-SA. (C) 1998 John Wiley & S ons, Inc. J Comput Chem 19: 1470-1481, 1998.