On the multiple-minima problem in the conformational analysis of polypeptides. I. Backbone degrees of freedom for a perturbed alpha-helix.

Abstract

The multiple-minima problem is the most formidable in the conformational analysis of polypeptides. Several approaches have been developed to surmount this problem, and we present an additional one here that may possibly be extendable to very large polypeptides. In this new approach, designated the Self-Consistent Electric Field (SCEF) method, we calculate the electric field, due to the whole molecule, at each CO and NH group of the peptide units, and also in the middle of the C′N peptide bonds, for an arbitrary starting conformation. It is assumed that the native conformation has approximately optimal orientations of its group dipoles in the electric field. The direction of the electric field with respect to the CO and NH bond dipole moments provides information as to which peptide units are the worst oriented. We then compute the changes in the backbone dihedral angles ϕ and ψ required to align the most unfavorably oriented peptide-unit dipole moments along the electric field. After carrying out such alignment of dipoles, a complete potential energy function is used in a minimization procedure to locate the nearest local minimum. The SCEF and energy-minimization procedures are then applied iteratively to try to locate the global minimum. The effectiveness of this method is illustrated by computations on very different starting conformations of terminally blocked 19-residue chains of poly(L-alanine), for which the global minimum is judged to be the right-handed α-helix.