Study On The Interaction Of Some Phytoestrogens With ER_α And ER_β Proteins By Molecular Dynamics Simulation

Phytoestrogens can exert estrogen-like and/or anti-estrogen effects with small side effects.Thus,researches on such compounds have continued to increase in recent years.Phytoestrogens exert estrogen-like effects by binding to estrogen receptor proteins,so it is important to study the interaction between the phytoestrogens and the estrogen receptors.In this study,the binding affinities and interactions between the typical phytoestrogens and the estrogen receptors were explored by molecular docking and molecular dynamics simulation method.The content of the paper is as follows:1.Resveratrol as one of the stilbene phytoestrogens,has high application value.Molecular docking and molecular dynamics simulations were used to explore the interaction between the two estrogen receptor subtypes(estrogen receptorα,ER_α;estrogen receptorβ,ER_β)and resveratrol as well as 17β-estradiol.The results of dynamics trajectory analysis showed that the system has reached a steady state after molecular dynamics simulation.Compared with 17β-estradiol,the binding ability of resveratrol to ER_αand ER_βwas less than that of 17β-estradiol.The binding mode indicated that hydrogen bonding and hydrophobic interactions play a certain stabilizing role in the process of ligand-receptor binding.The calculation and decomposition results of binding free energy showed that van der Waals energy and electrostatic energy contribute more to the total binding free energy.2.Three typical isoflavone phytoestrogens including genistein,daidzein and formononetin,with similar chemical structures,were docked with ER_αand ER_β,followed by the molecular dynamics simulations,respectively.Molecular docking and dynamics simulation results showed that the order of the affinity of the three isoflavone phytoestrogens and 17β-estradiol is:17β-estradio l>genistein>daidzein>formononetin.And its affinity for ER_βwas higher than that for ER_α.The calculation and decomposition of binding free energy indicated that van der Waals energy,electrostatic interaction,and non-polar solvation can promote the binding of the receptor to the ligand,while polar solvation can play the opposite role.3.Coumestrol,4-methoxycoumestrol,psoralen and isopsoralen belongs to the coumarin phytoestrogens with special structures.The binding affinity and interaction with ER_αand ER_βwere studied by molecular docking and molecular dynamics simulation methods.The calculation results showed that the four coumarin phytoestrogens have weaker affinities to ER_αand ER_βthan 17β-estradiol,and the affinity of4-methoxycoumestrol and coumestrol was significantly higher than that of psoralen and isopsoralen.In addition,the binding mode indicated that hydrogen bonding interactions and hydrophobic interactions have important effects on the stability of the complexes.4.The affinities of four lignan phytoestrogens,which belongs to plant lignans(matairesinol and secoisolarlciresinol)and animal lignans(enteroctone and enteroldiol),to ER_αand ER_βwere investigated by molecular dynamics simulations methords.The analysis results showed that the binding affinities of the four lignan phytoestrogens to ER_βwere higher than those to ER_α,and the affinities of plant lignans(matairesinol and secoisolarlciresinol)were higher than those of animal lignan(enteroctone and enteroldiol).