Oligomerization of amyloid Abeta16-22 peptides using hydrogen bonds and hydrophobicity forces

Biophys J. 2004 Dec;87(6):3657-64. doi: 10.1529/biophysj.104.046839. Epub 2004 Sep 17.

Abstract

The 16-22 amino-acid fragment of the beta-amyloid peptide associated with the Alzheimer's disease, Abeta, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of Abeta16-22 peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three, and six Abeta16-22 peptides. We find that the isolated Abeta16-22 peptide is mainly a random coil in the sense that both the alpha-helix and beta-strand contents are low, whereas the three- and six-chain systems form aggregated structures with a high beta-sheet content. Furthermore, in agreement with experiments on Abeta16-22 fibrils, we find that large parallel beta-sheets are unlikely to form. For the six-chain system, the aggregated structures can have many different shapes, but certain particularly stable shapes can be identified.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / chemistry*
  • Binding Sites
  • Computer Simulation
  • Dimerization
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Models, Chemical*
  • Models, Molecular*
  • Multiprotein Complexes / analysis
  • Multiprotein Complexes / chemistry
  • Peptide Fragments / analysis*
  • Peptide Fragments / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Stress, Mechanical
  • Temperature

Substances

  • Amyloid beta-Peptides
  • Multiprotein Complexes
  • Peptide Fragments
  • amyloid beta-protein (16-22)