Oligomerization of amyloid Abeta peptides using hydrogen bonds and hydrophobicity forces

The 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 αhelix and β-strand contents are low, whereas the threeand 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. ∗E-mail: favrin, anders, [email protected]