Understanding beta-hairpin formation

Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9068-73. doi: 10.1073/pnas.96.16.9068.

Abstract

The kinetics of formation of protein structural motifs (e.g., alpha-helices and beta-hairpins) can provide information about the early events in protein folding. A recent study has used fluorescence measurements to monitor the folding thermodynamics and kinetics of a 16-residue beta-hairpin. In the present paper, we obtain the free energy surface and conformations involved in the folding of an atomistic model for the beta-hairpin from multicanonical Monte Carlo simulations. The results suggest that folding proceeds by a collapse that is downhill in free energy, followed by rearrangement to form a structure with part of the hydrophobic cluster; the hairpin hydrogen bonds propagate outwards in both directions from the partial cluster. Such a folding mechanism differs from the published interpretation of the experimental results, which is based on a helix-coil-type phenomenological model.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Calorimetry
  • Computer Graphics
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Protein Conformation*
  • Protein Structure, Secondary*
  • Proteins / chemistry*
  • Software
  • Thermodynamics

Substances

  • Peptides
  • Proteins