MODELING COMPACT DENATURED STATES OF PROTEINS

We propose a model for the conformations of compact denatured states o f globular proteins: that they are broad ensembles of chain backbone c onformations that involve common localized hydrophobic clustering and helical contacts, depending on the amino acid sequence. We construct r epresentative ensembles for chain lengths up to 136 monomers on three- dimensional cubic lattices using the ''hydrophobic zippers'' method (F iebig and Dill, 1993). We find that model conformations with radii of gyration about 20% larger than native conformations commonly have bimo dal distributions of P(r), of the pairwise interatomic distances, r, a nd Kratky plots in agreement with recent small-angle X-ray scattering (Sosnick and Trewhella, 1992; Flanagan et al., 1992; Kataoka et al., 1 993; Flanagan et al., 1993) experiments on three different proteins. W e also find that the lattice model of the Shortle 1-136 fragment of st aphylococcal nuclease does not appear capable of forming a single hydr ophobic core by hydrophobic zippering, consistent with experiments.