A metastable state in folding simulations of a protein model

Nat Struct Biol. 1998 Mar;5(3):236-41. doi: 10.1038/nsb0398-236.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computer Simulation*
  • Drug Stability
  • Entropy
  • Kinetics
  • Models, Molecular*
  • Protein Conformation*
  • Protein Folding*
  • Proteins / chemistry*
  • Thermodynamics

Substances

  • Proteins