Is protein folding hierarchic? II. Folding intermediates and transition states

Trends Biochem Sci. 1999 Feb;24(2):77-83. doi: 10.1016/s0968-0004(98)01345-0.


The folding reactions of some small proteins show clear evidence of a hierarchic process, whereas others, lacking detectable intermediates, do not. Evidence from folding intermediates and transition states suggests that folding begins locally, and that the formation of native secondary structure precedes the formation of tertiary interactions, not the reverse. Some notable examples in the literature have been interpreted to the contrary. For these examples, we have simulated the local structures that form when folding begins by using the LINUS program with nonlocal interactions turned off. Our results support a hierarchic model of protein folding.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Folding*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / genetics
  • Sequence Homology, Amino Acid
  • Thermodynamics


  • Proteins