Impact of Cu(ii) and Al(iii) on the conformational landscape of amyloidβ_1-42

Metal ions have been found to play an important role in the formation of extracellular β-amyloid plaques, a major hallmark of Alzheimer's disease. In the present study, the conformational landscape of Aβ₄₂with Al(iii) and Cu(ii) has been explored using Gaussian accelerated molecular dynamics. Both metals reduce the flexibility of the peptide and entail a higher structural organization, although to different degrees. As a general trend, Cu(ii) binding leads to an increased α-helix content and to the formation of two α-helices that tend to organize in a U-shape. By contrast, most Al(iii) complexes induce a decrease in helical content, leading to more extended structures that favor the appearance of transitory β-strands.