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

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 Aβ_17–42 fibril as well as Aβ_1–42 monomer, leading to disassembly of β-strands of Aβ_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.