Oligomerization of Amyloid A β16–22 Peptides Using Hydrogen Bonds and Hydrophobicity Forces

Abstract

The 16–22 amino-acid fragment of the β-amyloid peptide associated with the Alzheimer’s disease, A β, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of A β 16–22 peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three, and six A β 16–22 peptides. We find that the isolated A β 16–22 peptide is mainly a random coil in the sense that both the α-helix and β-strand contents are low, whereas the three- and six-chain systems form aggregated structures with a high β-sheet content. Furthermore, in agreement with experiments on A β 16–22 fibrils, we find that large parallel β-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.