Protein Science, Vol 2, Issue 10 1715-1731, Copyright © 1993 by Cold Spring Harbor Laboratory Press

ARTICLE

Prediction of protein conformation on the basis of a search for compact structures: Test on avian pancreatic polypeptide

A. LIWO, M. R. PINCUS, R. J. WAWAK, S. RACKOVSKY and H. A. SCHERAGA
Baker Laboratory of Chemistry, Cornell University, Ithaca, New York 14853-1301 On leave from the Department of Chemistry, University of Gdansk, ul. Sobieskiego 18, 80-952 Gdansk, Poland, 1990-1992. Contact A. Liwo for computer programs.

Based on the concept that hydrophobic interactions cause a polypeptide chain to adopt a compact structure, a method is proposed to predict the 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 extensively using specially designed interactions to lead to a collapsed structure, (2) conversion of the lowest-energy virtual-bond united-residue chain to one with a real polypeptide backbone, with optimization of the hydrogen-bond network among the backbone groups, (3) perturbation of the latter structure by the electrostatically driven Monte Carlo (EDMC) procedure, and (4) conversion of the spherical representation of the 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 portion of the chain in an extended conformation packed against the {alpha}-helix. Similar structures with slightly higher energies, but looser packing, were also obtained.
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