New Techniques for the Construction of Residue Potentials for Protein Folding

. A smooth empirical potential is constructed for use in off-lattice protein folding studies. Our potential is a function of the amino acid labels and of the distances between the C ff atoms of a protein. The potential is a sum of smooth surface potential terms that model solvent interactions and of pair potentials that are functions of a distance, with a smooth cutoff at 12 Angstrom. Techniques include the use of a fully automatic and reliable estimator for smooth densities, of cluster analysis to group together amino acid pairs with similar distance distributions, and of quadratic programming to find appropriate weights with which the various terms enter the total potential. For nine small test proteins, the new potential has local minima within 1.3--4.7 A of the PDB geometry, with one exception that has an error of 8.5 A. Keywords. protein folding, tertiary structure, potential energy surface, global optimization, empirical potential, residue potential, surface potential, parameter..