Abstract
One of the main causes for Alzheimer disease is the abnormal self-assembly of the amyloid-beta (A beta) peptide, which in turn forms a toxic beta-rich aggregation. A recent study suggests that gold nanoparticles (AuNPs) can inhibit the A beta aggregation. Nevertheless, the effects of AuNPs on A beta peptide system are still ambiguous and needs exploration that is more detailed. Molecular dynamics simulations have been carried out to investigate the aggregation mechanism of A beta 42 peptide for 500 ns. During simulation, C-terminus regions of Met 35-Ala42 residues exhibits beta-sheet conformations. Meanwhile, the Au144MC coordination induces substantial alpha-helical character, both alpha-helix and 310-helix structure at 0-500ns, in the region of Asp1-Arg5 and Val36-Ile41 residues. The Au144MC strongly coordinates with Asp1, Ala2, Glu3, Phe4, Asp7, Tyr10 and Gln15 residues that plays the significant effects to loss the beta-sheet geometry in the N-terminal region and it converted into random alpha-helix, turn and bend conformation. On comparing the RMSF of the A beta 42 peptide and A beta 42-Au144MC complex shows that the coordination of Au144MC results in greater rigidity of the A beta 42 peptide backbone regions with exemptions for the Asp1, Ala2, Glu3, Leu34, Ile41 and Ala42 residues due to the strong binding between the metal cluster and the CHC (Leu17- Ala21) region. The structural stability of the A beta 42 peptide and A beta 42-Au144MC complex is enhanced by the several intermolecular and intramolecular interactions and it was visibly revealed in the H-bond. From the above results, it is very evident that the Au144MC can be used as inhibitor agent for the oligomerization of A beta 42.