title: Insight into estrogenicity of phytoestrogens using in silico simulation.
abstract: 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 (ERalpha-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 ERalpha-LBD provided the information to develop the phytoestrogen derivatives as the preferred drug for ER positive breast cancer treatment.
authors.affiliation: Department of Bioinformatics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Takuya
authors.initials: T
authors.lastname: Kumamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Suganami
authors.forename: Waka
authors.initials: W
authors.lastname: Nakanishi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tamura
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D003198:Computer Simulation; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods*; D019277:Entropy; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D048789:Phytoestrogens / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D055672:Static Electricity; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013816:Thermodynamics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D047628:Estrogen Receptor alpha; D048789:Phytoestrogens; D013256:Steroids; C406602:deoxymiroestrol