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