MODELING COMPACT DENATURED STATES OF PROTEINS

被引:90
作者
LATTMAN, EE
FIEBIG, KM
DILL, KA
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143
[2] JOHNS HOPKINS UNIV,SCH MED,DEPT BIOPHYS & BIOPHYS CHEM,BALTIMORE,MD 21205
关键词
D O I
10.1021/bi00186a015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We propose a model for the conformations of compact denatured states of globular proteins: that they are broad ensembles of chain backbone conformations that involve common localized hydrophobic clustering and helical contacts, depending on the amino acid sequence. We construct representative ensembles for chain lengths up to 136 monomers on three-dimensional cubic lattices using the ''hydrophobic zippers'' method (Fiebig and Dill, 1993). We find that model conformations with radii of gyration about 20% larger than native conformations commonly have bimodal distributions of P(r), of the pairwise interatomic distances, r, and Kratky plots in agreement with recent small-angle X-ray scattering (Sosnick and Trewhella, 1992; Flanagan et al., 1992; Kataoka et al., 1993; Flanagan et al., 1993) experiments on three different proteins. We also find that the lattice model of the Shortle 1-136 fragment of staphylococcal nuclease does not appear capable of forming a single hydrophobic core by hydrophobic zippering, consistent with experiments.
引用
收藏
页码:6158 / 6166
页数:9
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