Searching for Foldable Protein Structures Using Optimized

During evolution, the effective interactions between re.yidues in a protein can be adjusted through mutations to allow the protein to fold to its native structure on an adequate time scale. We seek to address the question: Are there some structures that can be better optimized than others? Using exhaustive enumeration of the compact conformations of short proteins confined to simple lattices, wefind that the best structures are those that contain contacts rare in random structures, indicating the importance of nonlocal contacts for assisting the folding process. Certain structural motifs such as long p-hairpins, Greek-key motifs, and jelly rolls, commonly found in proteins of known structure, have a high degree of optimizability. Contrary to what might be expected, positive correlations between the various interactions reduce optimizability. The optimization procedure produces a correlated energy landscape, which might assist folding.