Constructing smooth potential functions for protein folding.

A protein folding potential function ideally has several properties: it favors the native conformations for a number of protein sequences over a variety of nonnative folds; it can guide the search over conformations for the native state; it reflects changes in stability of the native fold due to changes in sequence; and it is relatively insensitive to small changes in conformation. While these are not mutually incompatible goals, attaining one property does not ensure that the others are satisfied. Examples are given of simple potentials having one property but lacking others. A new functional form of a folding potential is described where interactions between all nonhydrogen atoms are used to estimate interresidue interactions and implicit solvation. Its parameters can be adjusted to satisfy the above properties at least for barnase and a few other proteins.