Ab initio fragment molecular orbital calculations on the specific interactions between amyloid-β peptides in an in vivo amyloid-β fibril

The accumulation of amyloid-beta (Aβ) fibrils in a brain has been recognized to contribute to the onset of Alzheimer's disease (AD). However, the relation between the structure of the aggregate and its toxicity to AD patients remains to be fully elucidated. A recent solid-state NMR analysis for the tissue obtained from the brains of AD patients revealed that the Aβ aggregates have only a single structure with three-fold symmetry. We here investigate the specific interactions between Aβ peptides in the aggregate, using ab initio fragment molecular orbital calculations, to explain why such a unique structure possesses significant stability. The results indicate that the interactions between the Aβ peptides of the stacked Aβ pair are stronger than those between the Aβ peptides of the trimer with three-fold symmetry. Furthermore, it is elucidated that the charged amino-acid residues of Aβ mainly contribute to the strong attractive interactions between the paired Aβ peptides.