Inhibition Mechanisms of (-)-Epigallocatechin-3-gallate and Genistein on Amyloid-beta 42 Peptide of Alzheimer's Disease via Molecular Simulations

The misfolding and self-assembly of amyloid-beta (A beta) peptides are one of the most important factors contributing to Alzheimer's disease (AD). This study aims to reveal the inhibition mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and genistein on the conformational changes of A beta 42 peptides by using molecular docking and molecular dynamics (MD) simulation. The results indicate that both EGCG and genistein have inhibitory effects on the conformational transition of A beta 42 peptide. EGCG and genistein reduce the ratio of beta-sheet secondary structures of A beta 42 peptide while inducing random coil structures. In terms of hydrophobic interactions in the central hydrophobic core of A beta 42 peptide, the binding affinities of EGCG are significantly larger in comparison with that of genistein. Our findings illustrate the inhibition mechanisms of EGCG and genistein on the A beta 42 peptides and prove that EGCG is a very promising inhibitor in impeding the conformational change of A beta 42 peptide.