AN EMPIRICAL ENERGY FUNCTION FOR THREADING PROTEIN-SEQUENCE THROUGH THE FOLDING MOTIF

In this paper we present a new residue contact potantial derived by st atistical analysis of protein crystal structures. This gives mean hydr ophobic and pairwise contact energies as a function of residue type an d distance interval. To test the accuracy of this potential we generat e model structures by ''threading'' different sequences through backbo ne folding motifs found in the structural data base. We find that conf ormational energies calculated by summing contact potentials show perf ect specificity in matching the correct sequences with each globular f olding motif in a 161-protein data set. They also identify correct mod els with the core folding motifs of hemerythrin and immunoglobulin McP C603 V1-domain, among millions of alternatives possible when we align subsequences with alpha-helices and beta-strands, and allow for variat ion in the lengths of intervening loops. We suggest that contact poten tials reflect important constraints on non-bonded interaction in nativ e proteins, and that ''threading'' may be useful for structure predict ion by recognition of folding motif.