LOCAL MOVES - AN EFFICIENT ALGORITHM FOR SIMULATION OF PROTEIN-FOLDING

We have enhanced genetic algorithms and Monte Carlo methods for simula tion of protein folding by introducing ''local moves'' in dihedral spa ce, A local move consists of changes in backbone dihedral angles in a sequential window while the positions of all atoms outside the window remain unchanged. We find three advantages of local moves: (1) For som e energy functions, protein conformations of lower energy are found; ( 2) these low energy conformations are found in fewer steps; and (3) th e simulations are less sensitive to the details of the annealing proto col. To distinguish the effectiveness of local move algorithm from the complexity of the energy function, we have used several different ene rgy functions, These energy functions include the Profile score (Bowie et al., Science 253:164-170, 1991), the knowledge-based energy functi on used by Bowie and Eisenberg 1994 (Proc. Natl. Acad. Sci. U.S.A, 91: 4434-4440, 1994), two energy terms developed as suggested by Sippl and coworkers (Hendlich et al., J. Mel. Biol. 216:167-180, 1990), and AMB ER (Weiner and Kollman, J. Comp. Chem. 2:287-303, 1981). Besides these energy functions we have used three energy functions that include kno wledge of the native structures: the RMSD from the native structure, t he distance matrix error, and an energy term based on the distance bet ween different residue types called DBIN, In some of these simulations the main advantage of local moves is the reduced dependence on the de tails of the annealing schedule, In other simulations, local moves are superior to other algorithms as structures with lower energy are foun d. (C) 1995 Wiley-Liss, Inc.