Impact of the Astaxanthin, Betanin, and EGCG Compounds on Small Oligomers of Amyloid Aβ40 Peptide

There is experimental evidence that the astaxanthin, betanin, and epigallocatechin-3-gallate (EGCG) compounds slow down the aggregation kinetics and the toxicity of the amyloid-beta (A beta) peptide. How these inhibitors affect the self-assembly at the atomic level remains elusive. To address this issue, we have performed for each ligand atomistic replica exchange molecular dynamic (REMD) simulations in an explicit solvent of the A beta(11-40) trimer from the U-shape conformation and MD simulations starting from A beta(1-40) dimer and tetramer structures characterized by different intra- and interpeptide conformations. We find that the three ligands have similar binding free energies on small A beta(40) oligomers but very distinct transient binding sites that will affect the aggregation of larger assemblies and fibril elongation of the A beta(40) peptide.