Modeling Compact Denatured States of Proteins

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 ensemb...

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Bibliographic Details
Published in:Biochemistry (Easton) 1994-05, Vol.33 (20), p.6158-6166
Main Authors: Lattman, Eaton E, Fiebig, Klaus M, Dill, Ken A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Chemical Phenomena
Chemistry, Physical
Cytochrome c Group - chemistry
Micrococcal Nuclease - chemistry
Models, Molecular
Peptide Fragments - chemistry
Plant Proteins - chemistry
Protein Conformation
Protein Denaturation
Proteins - chemistry
Ribonuclease, Pancreatic - chemistry
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Summary: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 & 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 & 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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00186a015