An extensive replica exchange molecular dynamics (REMD) simulation was performed to investigate the progress patterns of the inhibition of (-)-epigallocatechin-3-gallate (EGCG) on the Aβ16-22 hexamer. Structural variations of the oligomers without and with EGCG were monitored and analyzed in detail. It has been found that EGCG prevents the formation of Aβ oligomer through two different ways by either accelerating the Aβ oligomerization or reducing the β-content of the hexamer. It also decreases the potential "highly toxic" conformations of Aβ oligomer, which is related to the conformations having high order β-sheet sizes. Both electrostatic and van der Waals interaction energies are found to be involved to the binding process. Computed results using quantum chemical methods show that the π-π stacking is a critical factor of the interaction between EGCG and the peptides. As a result, the binding free energy of the EGCG to the Aβ peptides is slightly larger than that of the curcumin.
Keywords: Amyloid beta oligomer; EGCG; Free energy perturbation; Quantum calculation; Replica exchange molecular dynamics; π-stacking.
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