Fully flexible docking models of the complex between α7 nicotinic receptor and a potent heptapeptide inhibitor of the β-amyloid peptide binding

The heptapeptide IQTTWSR (IQ), recently reported as inhibitor of the β-amyloid (Aβ) binding to nicotinic acetylcholine receptors (nAChrs), was docked to the homology model of the α7 nicotinic acetylcholine receptor. The most representative models were further subjected to molecular dynamics simulations. The data obtained here suggest that Aβ needs highly specific structural motifs to bind to the α7nAChR. These structural motifs are located principally in the upper and lower surroundings of loop C, including loop F and sheets β1, β2, β6, β9, and β10 of the receptor. Overall, these results suggest that IQ can be mimicked by more bioavailable, stable compounds that would be helpful for the understanding of the Aβ binding site and its dynamics, and for the design of novel agents to be used as an effective alternative against Alzheimer’s disease.