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The interaction between Amyloid β (Aβ) peptide and acetylcholine receptor is the key for our understanding of how Aβ fragments block the ion channels within the synapses and thus induce Alzheimer’s disease. Here, molecular docking and molecular dynamics (MD) simulations were performed for the structural dynamics of the docking complex consisting of Aβ and α7-nAChR (α7 nicotinic acetylcholine receptor), and the inter-molecular interactions between ligand and receptor were revealed. The results show that Aβ25-35 is bound to α7-nAChR through hydrogen bonds and complementary shape, and the Aβ25-35 fragments would easily assemble in the ion channel of α7-nAChR, then block the ion transfer process and induce neuronal apoptosis. The simulated amide-I band of Aβ25-35 in the complex is located at 1650.5 cm−1, indicating the backbone of Aβ25-35 tends to present random coil conformation, which is consistent with the result obtained from cluster analysis. Currently existing drugs were used as templates for virtual screening, eight new drugs were designed and semi-flexible docking was performed for their performance. The results show that, the interactions between new drugs and α7-nAChR are strong enough to inhibit the aggregation of Aβ25-35 fragments in the ion channel, and also be of great potential in the treatment of Alzheimer’s disease.

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