title: The molecular mechanism of bisphenol A (BPA) as an endocrine disruptor by interacting with nuclear receptors: insights from molecular dynamics (MD) simulations.
abstract: Bisphenol A (BPA) can interact with nuclear receptors and affect the normal function of nuclear receptors in very low doses, which causes BPA to be one of the most controversial endocrine disruptors. However, the detailed molecular mechanism about how BPA interferes the normal function of nuclear receptors is still undiscovered. Herein, molecular dynamics simulations were performed to explore the detailed interaction mechanism between BPA with three typical nuclear receptors, including hERα, hERRγ and hPPARγ. The simulation results and calculated binding free energies indicate that BPA can bind to these three nuclear receptors. The binding affinities of BPA were slightly lower than that of E2 to these three receptors. The simulation results proved that the binding process was mainly driven by direct hydrogen bond and hydrophobic interactions. In addition, structural analysis suggested that BPA could interact with these nuclear receptors by mimicking the action of natural hormone and keeping the nuclear receptors in active conformations. The present work provided the structural evidence to recognize BPA as an endocrine disruptor and would be important guidance for seeking safer substitutions of BPA.
authors: School of Pharmacy, Lanzhou University, Lanzhou, China.
authors: Lanlan
authors: L
authors: Li
authors: School of Pharmacy, Lanzhou University, Lanzhou, China.
authors: Qianqian
authors: Q
authors: Wang
authors: School of Pharmacy, Lanzhou University, Lanzhou, China.
authors: Yan
authors: Y
authors: Zhang
authors: State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou, China.
authors: Yuzhen
authors: Y
authors: Niu
authors: State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China.
authors: Xiaojun
authors: X
authors: Yao
authors: School of Pharmacy, Lanzhou University, Lanzhou, China; Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, China.
authors: Huanxiang
authors: H
authors: Liu
mesh_terms: D000595:Amino Acid Sequence; D001559:Benzhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000737:chemistry* / Q000378:metabolism; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D047495:PPAR gamma; D010636:Phenols; D011960:Receptors, Estrogen; C490917:ESRRG protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds