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Oligomerization of amyloid Abeta peptides using hydrogen bonds and hydrophobicity forces

Giorgio Favrin·Anders Irbäck·Sandipan Mohanty
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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.

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Giorgio Favrin, Anders Irbäck, Sandipan Mohanty. 2004-09-14. Oligomerization of amyloid Abeta peptides using hydrogen bonds and hydrophobicity forces. https://doi.org/10.1529/biophysj.104.046839

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