Effects of natural compounds on conformational properties and hairpin formation of amyloid-β₄₂ monomer: docking and molecular dynamics simulation study

Abstract

The β₄₂ amyloid peptides (Aβ) are identified as a candidate target for Alzheimer’s drugs. Phenolic compounds can bind to the Aβ and inhibit amyloid formation. However, the inhibitory mechanism of phenolic compounds remains unclear. In this study, the molecular dynamic simulation and docking program were used to characterize the molecular details of inhibitory mechanism of the phenolic compounds. Our Results show that the phenolic compounds can bind to hydrophobic region in Aβ₄₂ monomer and alter hydrophobic interactions network at Aβ₄₂ which play a key role in β-sheet formation. The cluster analysis and interactions network analysis were used to probe conformational changes in Aβ₄₂. In most populated clusters of Aβ₄₂-phenolic compounds complexes, the sheet structures were not observed or reduced. It seems that the binding of phenolic compounds can induce larger conformational diversity for amyloid peptide and changes conformational properties of amyloid peptide. The phenolic compounds can deform β-Hairpin structure of Aβ by destabilizing salt bridges E22-K28 and D23-K28 which can alter the conformation of Aβ₄₂ in aqueous solution. These findings are in accordance with experimental results, to some extent give a molecular level interpretation for the inhibitory mechanism of phenolic compounds .In addition, this study may add important new details to the inhibitory mechanism of Alzheimer’s drug.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

KEYWORD:

• Amyloid formation
• phenolic compound
• Alzheimer’s drug

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research has been supported by the Iranian National Science Foundation (INSF), 96006759, and Tarbiat Modares Research grant, IG-39708.