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

Abstract

Alzheimer's disease is a neurodegenerative and incurable disease that is associated with the amyloid beta (Aβ) aggregation. We have carried out comparative molecular dynamics simulations of a 6-mer peptide and its analogues to elucidate the inhibitory mechanism on Aβ aggregation. The top analogue screened after refinement via docking exhibited significant inhibitory activities on both Aβ17-42 fibril as well as Aβ1-42 monomer, leading to disassembly of β-strands of Aβ1-42 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.