基于分子对接技术研究双酚类化合物与雌激素受体相互作用  

The interaction between bisphenol compounds and estrogen receptor based on molecular docking

作　　者：何昊祺 刘仪娃 曹静怡 李海朋 邓松 潘琪 李丽 石明 HE Haoqi;LIU Yiwa;CAO Jingyi;LI Haipeng;DENG Song;PAN Qi;LI Li;SHI Ming(School of Public Health,Guangdong Medical University,Dongguan Key Laboratory of Environmental Medicine,Dongguan,Guangdong 523808,China)

机构地区：[1]广东医科大学公共卫生学院,东莞市环境医学重点实验室,广东东莞523808

出　　处：《中国职业医学》2024年第3期265-271,共7页China Occupational Medicine

基　　金：国家自然科学基金面上项目(82373615);广东医科大学学科建设类“临床+基础”专项项目(4SG24006G)。

摘　　要：目的 探讨双酚A及其替代物的雌激素干扰效应,分析相关作用机制。方法 选择双酚A和目前应用最广泛的3种双酚A替代物双酚S、双酚F和双酚AF作为对接的配体分子,并以雌二醇为对照配体分子,采用AutoDock软件将其与雌激素受体(ER)α和ERβ进行分子对接。结果 双酚A与ERα可结合形成1个氢键,位于His474残基处;双酚A与ERβ结合可形成3个氢键,分别位于Leu260、His428和Asn431处。与双酚A类似,双酚S、双酚F、双酚AF和雌二醇主要通过疏水作用力和氢键与ERα和ERβ进行相互作用,但最佳结合位点和结合力有所不同。双酚A、双酚F、双酚AF、双酚S和雌二醇与ERα的最佳结合位点的结合能分别为-4.15、-4.19、-2.73、-4.62和-5.37 kcal/mol,与ERβ的结合能分别为-3.76、-3.91、-2.86、-3.93和-4.98 kcal/mol。2种ERs与上述5种分子的结合力从高到低依次为雌二醇>双酚S>双酚F>双酚A>双酚AF。结论 双酚类化合物与ERα和ERβ的结合亲和力主要由与受体非极性残基间的疏水性作用、与关键残基形成氢键提供。双酚S、双酚F和双酚AF表现出了与双酚A类似甚至更强的内分泌干扰效应。Objective To investigate the anti-estrogenic activity of bisphenol A and its substitutes, and to analyze the relevant mechanisms. Methods Bisphenol A and its three most widely used substitutes(bisphenol S, bisphenol F and bisphenol AF) were selected as the docking ligand molecules, and estradiol was used as the control ligand molecule. The ligand molecules docking was simulated with estrogen receptor(ER) α and ERβ using AutoDock software. Results Bisphenol A forms a hydrogen bond with ERα at the His474 residue and with ERβ via three hydrogen bonds at Leu260, His428, and Asn431residues. Similar to bisphenol A, bisphenol S, bisphenol F, bisphenol AF and estradiol primarily interact with ERα and ERβthrough hydrophobic interactions and hydrogen bonds, but with varying optimal binding sites and affinities. The binding forces of the optimal binding sites for bisphenol A, bisphenol F, bisphenol AF, bisphenol S and estradiol with ERα were-4.15,-4.19,-2.73,-4.62 and-5.37 kcal/mol, respectively, and with ERβ were-3.76,-3.91,-2.86,-3.93, and-4.98 kcal/mol, respectively. The affinity ranking for two ERs with these five molecules from high to low was estradiol > bisphenol S> bisphenol F>bisphenol A > bisphenol AF. Conclusion The affinity between bisphenol compounds with ERα and ERβ is mainly based on the hydrophobic interaction with non-polar residues of the receptor and hydrogen bonding with key residues. Bisphenol S, bisphenol F and bisphenol AF showed similar or even stronger endocrine disrupting effects than bisphenol A.

关 键 词：分子对接 双酚类化合物 雌激素受体 雌二醇 

分 类 号：R135.99[医药卫生—劳动卫生] R114[医药卫生—公共卫生与预防医学]