In silico assembly of Alzheimer's Abeta16-22 peptide into beta-sheets

J Am Chem Soc. 2004 Sep 22;126(37):11509-16. doi: 10.1021/ja047286i.

Abstract

Recent studies suggest that soluble oligomers of amyloid-forming peptides have toxic effects in cell cultures. In this study, the folding of three Alzheimer's A beta(16-22) peptides have been simulated with the activation-relaxation technique and a generic energy model. Starting from randomly chosen states, the predicted lowest energy structure superposes within 1 A rms deviation from its conformation within the fibrils. This antiparallel structure is found to be in equilibrium with several out-of-register antiparallel beta-sheets and mixed parallel-antiparallel beta-sheets, indicating that full structural order in the fibrils requires larger aggregates. Folding involves the formation of dimers followed by the addition of a monomer and proceeds through a generalized mechanism between disordered and native alignments of beta-strands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Computer Simulation
  • Models, Chemical
  • Models, Molecular
  • Peptide Fragments / chemistry*
  • Protein Folding
  • Protein Structure, Secondary
  • Thermodynamics

Substances

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