PREDICTION OF PROTEIN CONFORMATION ON THE BASIS OF A SEARCH FOR COMPACT STRUCTURES - TEST ON AVIAN PANCREATIC-POLYPEPTIDE

Based on the concept that hydrophobic interactions cause a polypeptide chain to adopt a compact structure, a method is proposed to predict t he structure of a protein. The procedure is carried out in four stages : (1) use of a virtual-bond united-residue approximation with the side chains represented by spheres to search conformational space extensiv ely using specially designed interactions to lead to a collapsed struc ture, (2) conversion of the lowest-energy virtual-bond united-residue chain to one with a real polypeptide backbone, with optimization of th e hydrogen-bond network among the backbone groups, (3) perturbation of the latter structure by the electrostatically driven Monte Carlo (EDM C) procedure, and (4) conversion of the spherical representation of th e side chains to real groups and perturbation of the whole molecule by the EDMC procedure using the empirical conformational energy program for peptides (ECEPP/2) energy function plus hydration. Application of this procedure to the 36-residue avian pancreatic polypeptide led to a structure that resembled the one determined by X-ray crystallography; it had an alpha-helix starting at residue 13, with the N-terminal por tion of the chain in an extended conformation packed against the alpha -helix. Similar structures with slightly higher energies, but looser p acking, were also obtained.