Molecular docking of four β-amyloid _1-42 fragments on the α7 nicotinic receptor: Delineating the binding site of the Aβ peptides

Three-dimensional structures of the complexes between the Aβ _1-42 fragments Aβ _1-11, Aβ _10-20, Aβ _12-28, and Aβ _22-35 and the α7 nicotinic receptor were obtained with the aid of the ESCHER program. Furthermore, short high-temperature molecular dynamics simulations in vacuo were employed to relax the complexes and allow the peptides to accommodate in the binding site. The final models have shown that Aβ peptides do bind on the same site, which is delineated by loop C of one subunit and the loops 62-74 and G of the adjacent subunit on the receptor. This finding is supported by previous experimental and theoretical data, and should help one to obtain a better and more detailed structural information about the activity of the Aβ peptides and their repercussion in the disorders at molecular level, which are characteristic of the Alzheimer's disease.