MONTE-CARLO SIMULATIONS OF PROTEIN-FOLDING .1. LATTICE MODEL AND INTERACTION SCHEME

A new hierarchical method for the simulation of the protein folding pr ocess and the de novo prediction of protein three-dimensional structur e is proposed. The reduced representation of the protein alpha-carbon backbone employs lattice discretizations of increasing geometrical res olution and a single ball representation of side chain rotamers. In pa rticular, coarser and finer lattice backbone descriptions are used. Th e coarser (finer) lattice represents Calpha traces of native proteins with an accuracy of 1.0 (0.7) angstrom rms. Folding is simulated by me ans of very fast Monte Carlo lattice dynamics. The potential of mean f orce, predominantly of statistical origin, contains several novel term s that facilitate the cooperative assembly of secondary structure elem ents and the cooperative packing of the side chains. Particular contri butions to the interaction scheme are discussed in detail. In the acco mpanying paper (Kolinski, A., Skolnick, J. Monte Carlo simulation of p rotein folding. II. Application to protein A, ROP, and crambin. Protei ns 18:353-366, 1994), the method is applied to three small globular pr oteins. (C) 1994 Wiley-Liss, Inc.