Characterizing the first steps of amyloid formation for the ccbeta peptide

J Phys Chem B. 2008 Aug 14;112(32):9998-10004. doi: 10.1021/jp801222x. Epub 2008 Jul 23.


We employ constant-temperature and replica exchange molecular dynamics to survey the free energy landscape of the ccbeta peptide using a united-atom potential and an implicit solvent representation. Starting from the experimental coiled-coil structure we observe alpha to beta conversion on increasing the temperature, in agreement with experiment. Various beta-sheet trimers are identified as free energy minima, including one that closely resembles the amyloid beta-sheet model previously proposed from experimental data. We characterize two alternative pathways leading to beta-sheets. The first proceeds via direct alpha to beta conversion without dissociation of the trimer, and the second can be classified as a dissociation/reassociation pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / biosynthesis*
  • Amyloid / chemistry
  • Biopolymers / chemistry
  • Molecular Structure
  • Peptides / chemistry*


  • Amyloid
  • Biopolymers
  • Peptides