It is widely accepted that the addition of zinc leads to the formation of neurotoxic nonfibrillar aggregates of beta-amyloid peptides Aβ
40 and Aβ
42 and at the same time destabilizes amyloid fibrils. However, the mechanism of the effect of zinc on beta-amyloid is not fully understood. In this study, a fast zinc-induced aggregation of Aβ
16 (as compared to a system without zinc) via the formation of Aβ
16 dimers with one zinc ion coordinated in the metal-binding site
11EVHH
14, followed by their polymerization, has been studied by molecular dynamics. The best aggregation was shown by the system composed of Aβ
16 dimers bound by one zinc ion, with no additional zinc in solution. The presence of Aβ
16 dimers was a major condition, sufficient for fast aggregation into larger complexes. It has been shown that the addition of zinc to a system with already formed dimers does not substantially affect the characteristics and rate of aggregation. At the same time, an excessive concentration of zinc at the early stages of the formation of conglomerates can negatively affect aggregation, since in systems where zinc ions occupied the
11EVHH
14 coordination center and the His6 residue of every Aβ
16 monomer, the aggregation proceeded more slowly and the resulting complexes were not as large as in the zinc-free Aβ system. Thus, this study has shown that the formation of Aβ
16 dimers bound through zinc ions at the
11EVHH
14 sites of the peptides plays an important role in the formation of neurotoxic non-fibrillar aggregates of beta-amyloid peptide Aβ
16. The best energetically favorable structure has been obtained for the complex of two Aβ
16 dimers with two zinc ions.
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