Molecular docking studies of dioxins with human estrogen receptors

Dioxins are classified by World Health Organization (WHO) as one of the dangerous chemical groups due to its highly toxic potential. In human, long term exposure of dioxins are associated with immune system, reproductive and developmental problems, as well as cancer. In this study, we used molecular docking method to study binding of dioxins to estrogen receptor -α and -β. The results show all dioxins bound to two binding pockets of estrogen receptor structure in agonistic and antagonistic states. In the primary binding pocket (the known binding pocket of nuclear receptor family), dioxins bound with average affinity of -6.9 kcal/mol. 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin exhibited the highest binding affinity of -8.3 kcal/mol. In the secondary binding pocket (the binding pocket of second hydroxytamoxifen), the highest binding affinity of dioxin were seen with 1,2,3,6, 7 ,8- hexachlorodibenzo-p-dioxin (HxCDD) with a binding affinity of -6.3 kcal/mol. Furthermore, docking of known ligands, estradiol (human estrogen) and genistein (plant estrogen) showed similar binding affinity. In conclusion, the results indicate that dioxins potentially bind to estrogen receptors and act as endocrine disruptors.