Dynamics and fluidity of amyloid fibrils: a model of fibrous protein aggregates

J Am Chem Soc. 2002 Dec 25;124(51):15150-1. doi: 10.1021/ja0273290.

Abstract

A previous experimentally defined model for the fibril formed from the core residues of the beta-amyloid (Abeta) peptides of Alzheimer's disease, 10YEVHHQKLVFFAEDVGSNKGAIIGLM, Abeta(10-35) using spectroscopic and scattering analyses reports on the average structure, benefiting immensely from the homogeneous assembly of Abeta(10-35). However, the energetic constraints that contribute to fibril dynamics and stability remain poorly understood. Here we perform molecular dynamics simulations to extend the structural assignment by providing evidence for a dynamic average ensemble with transient backbone H-bonds and internal solvation contributing to the inherent stability of amyloid fibrils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Computer Simulation
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Protein Structure, Secondary

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (10-35)