EGCG inhibits the oligomerization of amyloid beta (16-22) hexamer: Theoretical studies

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 A beta(16-22) 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 A beta oligomer through two different ways by either accelerating the A beta oligomerization or reducing the beta-content of the hexamer. It also decreases the potential "highly toxic" conformations of A beta oligomer, which is related to the conformations having high order beta-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 pi-pi 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 A beta peptides is slightly larger than that of the curcumin. (C) 2017 Elsevier Inc. All rights reserved.