A comparative study to elucidate the inhibitory mechanism of a 6-mer fragment of amyloid-beta 42 peptide as a potential therapeutic in Alzheimer's disease: insights from molecular dynamics simulations

摘要

Alzheimer's disease is a neurodegenerative and incurable disease that is associated with the amyloid beta (A beta) aggregation. We have carried out comparative molecular dynamics simulations of a 6-mer peptide and its analogues to elucidate the inhibitory mechanism on A. aggregation. The top analogue screened after refinement via docking exhibited significant inhibitory activities on both A beta(17-42) fibril as well as A beta(1-42) monomer, leading to disassembly of beta-strands of A beta(1-42) peptide and fibril by interacting with C-terminal residues via hydrogen bonds and hydrophobic contacts. Binding of the analogue to the C-terminal region proves to be significant.