Oligomerization of Amyloid Aβ16–22 Peptides Using Hydrogen Bonds and Hydrophobicity Forces

AbstractThe 16–22 amino-acid fragment of the β-amyloid peptide associated with the Alzheimer’s disease, Aβ, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of Aβ16–22 peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three, and six Aβ16–22 peptides. We find that the isolated Aβ16–22 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 Aβ16–22 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