PMID: 9501918Mar 21, 1998

A metastable state in folding simulations of a protein model

Nature Structural Biology
A R Dinner, M Karplus

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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Citations

Mar 21, 2003·Biophysical Chemistry·T Lazaridis, M Karplus
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Related Concepts

In Silico
Drug Stability
Protein Conformation
Thermodynamics
Protein Folding, Globular
Entropy

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