Molecular insight into amyloid oligomer destabilizing mechanism of flavonoid derivative 2-(4′ benzyloxyphenyl)-3-hydroxy-chromen-4-one through docking and molecular dynamics simulations

Results showed different preferred binding sites of compound 1 and good affinity toward the target. Through the course of 35 ns molecular dynamics simulation, conformations_5 of compound 1 intercalates into the hydrophobic core near the salt bridge and showed major structural changes as compared to other conformations. Compound 1 showed interference with the salt bridge and thus reducing the inter strand hydrogen bound network.

This minimizes the side chain interaction between the chains A–B leading to disorder in oligomer. Contact map analysis of amino acid residues between chains A and B also showed lesser interaction with adjacent amino acids in the presence of compound 1 (conformations_5). The study provides an insight into how compound 1 interferes and disorders the Aβ peptide.

These findings will further help to design better inhibitors for aggregation of the amyloid oligomer.