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A metastable state in folding simulations of a protein model

Nature Structural Biology volume 5, pages 236–241 (1998)Cite this article

Abstract

The native state of a protein is generally believed to be the global free energy minimum. However, there is increasing evidence that kinetically selected states play a role in the biological function of some proteins. In a recent folding study of a 125-residue heteropolymer model, one of 200 sequences was found to fold repeatedly to a particular local minimum that did not interconvert to the global minimum. The kinetic preference for this ‘metastable’ state is shown to derive from an entropic barrier associated with inserting a tail segment into the protein interior of the serpin-like global minimum structure. The relation of the present results to the role of metastable states in functioning and pathogenic proteins is discussed.

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Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts, 02138, USA

    Aaron R. Dinner & Martin Karplus

  2. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts, 02138, USA

    Aaron R. Dinner & Martin Karplus

  3. Laboratoire de Chimie Biophysique, Institut le Bel, Université Louis Pasteur, 4 Rue Blaise Pascal, 67000, Strasbourg, France

    Martin Karplus

Authors
  1. Aaron R. Dinner
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  2. Martin Karplus
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Correspondence to Martin Karplus.

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Dinner, A., Karplus, M. A metastable state in folding simulations of a protein model. Nat Struct Mol Biol 5, 236–241 (1998). https://doi.org/10.1038/nsb0398-236

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