We have enhanced genetic algorithms and Monte Carlo methods for simulation of protein folding by introducing “local moves” in dihedral space. 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 some energy functions, protein conformations of lower energy are found; (2) these low energy conformations are found in fewer steps; and (3) the simulations are less sensitive to the details of the annealing protocol. To distinguish the effectiveness of local move algorithm from the complexity of the energy function, we have used several different energy functions. These energy functions include the Profile score (Bowie et al., Science 253:164–170, 1991), the knowledge-based energy function 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. Mol. Biol. 216:167180, 1990), and AMBER (Weiner and Kollman, J. Comp. Chem. 2:287-303, 1981). Besides these energy functions we have used three energy functions that include knowledge of the native structures: the RMSD from the native structure, the distance matrix error, and an energy term based on the distance between different residue types called DBIN. In some of these simulations the main advantage of local moves is the reduced dependence on the details of the annealing schedule. In other simulations, local moves are superior to other algorithms as structures with lower energy are found. © 1995 Wiley-Liss, Inc.