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

Abstract

The misfolding and self-assembly of amyloid-beta (Aβ) 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 Aβ42 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 Aβ42 peptide. EGCG and genistein reduce the ratio of β-sheet secondary structures of Aβ42 peptide while inducing random coil structures. In terms of hydrophobic interactions in the central hydrophobic core of Aβ42 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 Aβ42 peptides and prove that EGCG is a very promising inhibitor in impeding the conformational change of Aβ42 peptide.

Insights into Molecular Mechanisms of EGCG and Apigenin on Disrupting Amyloid-Beta Protofibrils Based on Molecular Dynamics Simulations

“…Thus, we conclude that the van der Waals interactions between Aβ42 protofibril and EGCG are dominant in the binding free energy, which is in accord with a recent computational study. 63 In contrast to EGCG, apigenin has weak hydrophobic interactions with the Aβ42 protofibril, but the electrostatic interactions between Aβ42 protofibril and apigenin make a major contribution to the binding affinity.…”

Global Analysis of Plasmodium falciparum Dihydropteroate Synthase Variants Associated with Sulfadoxine Resistance Reveals Variant Distribution and Mechanisms of Resistance: A Computational-Based Study

“…Changes in the Gibbs free energy of mutations I431V, A437G, K540E, A581G, A613S, A437G/A581G, and A437G/A581G/A613S revealed a destabilization effect around the regions of the active site resulting from the loss of hydrogen bonds in neighboring residues. The destabilization effect may suggest conformational changes, which could affect SDX binding [42,43].…”

New neuroprotective derivatives of cinnamic acid by biotransformation

“…Human neuroblastoma (SH-SY5Y) cells obtained from ATCC (Manassas, VA, USA) were cultured in Dulbecco's Modified Eagle's medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum, 20 mm glutamine, 10 U mL −1 penicillin and 100 μg mL −1 streptomycin (Gibco BRL, Gaithersburg, MD, USA) maintained at 37 °C under a humidified atmosphere with 5% CO 2 . Cells (2 × 10 4 cells per well) were incubated with different concentrations (25,50,100,150,200, 300 μM) of the tested compounds. After 24 h, cell viability was determined using the WST-1 reagent 45 (Sigma Aldrich, St Louis, MO, USA).…”

“…S22A †). So, cells (2 × 10 4 cells per well) were incubated with different concentrations (25,50, 100 μMthe non-cytotoxic concentrations) of the tested compounds or catechin as a positive control. 47 After two hours, 48,49 the media were replaced with fresh ones and the cells were treated with H 2 O 2 (150 μM) for 24 h. Finally, cell viability was evaluated as mentioned above.…”