Food flavonoid ligand structure/estrogen receptor-α affinity relationships - toxicity or food functionality?

In silico molecular modelling is used to study interactions between flavonoid phytoestrogens and estrogen receptor (ER)α. Twenty flavonoids from foods were studied; e.g., genistein from soy, naringenin from grapefruit, phloretin from pears, chrysin from oyster mushrooms. These potential ligands' molecular attributes and their spatial arrangements that favour binding to the ligand binding cleft (LBC) of ERα are identified, and Docking Scores calculated. The Docking Score order is the same as the estrogenicity order for 8 of the flavonoids studied in detail. The number and position of flavonoid ring hydroxyls influence the Docking Scores which might relate to ERα's bio-activity. Hydrophobic interactions between ligands and ERα are also important; the number of rotatable CC bonds in ligands likely affects the magnitude of hydrophobic interactions and ligand fit. Our findings suggest that flavonoids with diverse structural features could have different binding energies and binding affinities with ERα, which might confer different functionalities and toxicities.