Insight into estrogenicity of phytoestrogens using in silico simulation

Phytoestrogens, including miroestrol and deoxymiroestrol, have the ability to act through competition with estrogen for binding to the estrogen receptor (ER). Here, we utilize manual ligand docking followed by molecular dynamics simulations and binding free energy calculations with the linear interaction energy method to predict the binding modes and the binding affinities of phytoestrogens on the ligand binding domain of ER (ERα-LBD). The calculations brought about the good correlation between the calculated binding free energy and the bioassays. Furthermore, consideration of Lennard–Jones and Coulomb interaction energies of miroestrol and deoxymiroestrol on ERα-LBD provided the information to develop the phytoestrogen derivatives as the preferred drug for ER positive breast cancer treatment.