Oligomerization of amyloid Abeta peptides using hydrogen bonds and hydrophobicity forces

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 Abeta(16-22) peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three and six Abeta(16-22) peptides. We find that the isolated Abeta(16-22) 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 Abeta(16-22) 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.

19 pages, 7 figures (to appear in Biophys. J.)

References in corpus (4)

• Simulated Tempering: A New Monte Carlo Scheme
• Studies of an Off-Lattice Model for Protein Folding: Sequence Dependence and Improved Sampling at Finite Temperature
• Monte Carlo Update for Chain Molecules: Biased Gaussian Steps in Torsional Space
• Thermodynamics of alpha- and beta-structure formation in proteins

Cited by in corpus (6)

• Microcanonical Analyses of Peptide Aggregation Processes
• Probing the Mechanisms of Fibril Formation Using Lattice Models
• Folding thermodynamics of peptides
• Elongation dynamics of amyloid fibrils: a rugged energy landscape picture
• Fibril elongation mechanisms of HET-s prion-forming domain: Topological evidence for growth polarity
• Hydrogen bond models for the simulation of protein folding and aggregation