In silico exploration of hydroxylated polychlorinated biphenyls as estrogen receptor β ligands by 3D-QSAR, molecular docking and molecular dynamics simulations.

Abstract

Hydroxylated polychlorinated biphenyls (HO-PCBs), as the major metabolites of PCBs, have been reported to act as estrogen receptor β (ERβ) agonists. However, the chemical-biological interactions governing their activities toward ERβ have not been elucidated. Therefore, three dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations, to the best of our knowledge, for the first time were performed to explore the correlation between the structures and activities. The best 3D-QSAR model presented higher predictive ability (R2cv=0.543, R2pred=0.5793/R2cv=0.543, R2pred=0.6795) based on comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA), respectively. At the same time, the derived contour maps indicated the important structural features required for improving the activity. Furthermore, molecular docking studies and MD simulations predicted the binding mode and the interactions between the ligand and the receptor. All the results would lead to a better understanding of the specific mechanism of HO-PCBs on estrogen receptor β (ERβ).Communicated by Ramaswamy H. Sarma.