贝类雌激素受体的同源建模与分子对接研究  

Understanding Homology Modeling and Molecular Docking of Bivalve Estrogen Receptors

作　　者：刘力铷 苗晶晶 赵安冉 潘鲁青[1] LIU Li-Ru;MIAO Jing-Jing;ZHAO An-Ran;PAN Lu-Qing(The Key Laboratory of Mariculture(Ocean University of China), Ministry of Education, Qingdao 266003, China)

机构地区：[1]海水养殖教育部重点实验室(中国海洋大学),山东青岛266003

出　　处：《中国海洋大学学报（自然科学版）》2021年第6期17-25,共9页Periodical of Ocean University of China

基　　金：国家自然科学基金青年项目(31602164)资助。

摘　　要：采用多模板同源建模方法构建了斑马鱼(Danio rerio)、长牡蛎(Crassostrea gigas)和菲律宾蛤仔(Ruditapes philippinarum)雌激素受体配体结合区(ER-LBD)的三维结构模型,并开展了与苯并芘(B[a]P)、四溴双酚A(TBBPA)和对壬基酚(4-NP)的分子对接研究。采用PROCHECK、ERRAT和Verify3D软件对同源模型质量进行了综合评估。研究表明:三个模型具有良好的高分辨率结构(>95%),且被合理折叠和建构。分子对接模拟发现,在激活构象中上述配体分子位于两种贝类与鱼类ER的活性配体空腔中,配体结合能的稳定性顺序为B[a]P>TBBPA>4-NP。对接分析表明,与配体结合的三个模型配体口袋的氨基酸残基高度保守,其中在活性位点处结合的主要氨基酸残基为斑马鱼Glu321、Arg362,长牡蛎Glu290、Arg331和菲律宾蛤仔Glu242、Arg283。研究结果表明,通过探究氨基酸残基所构成的空腔和配体形成的静电相互作用网络,能够确定内分泌干扰物(EDCs)对ER的优选程度,为EDCs对贝类内分泌干扰效应研究提供了理论依据和技术支撑。Three-dimensional structural models of the ligand binding domain of estrogen receptor(ER-LBD)of zebrafish(Danio rerio),pacific oyster(Crassostrea gigas)and manila clam(Ruditapes phili-ppinarum)were constructed by multi-template homology modeling.Molecular docking studies with benzapyrene(BaP),tetrabromobisphenol A(TBBPA)and 4-nonyl phenol(4-NP)were subsequently performed.PROCHECK,ERRAT and Verify3D were used to comprehensively evaluate the quality of homology models.The results showed that the three models had good high-resolution structures(>95%),and were reasonably folded and constructed.Molecular docking simulations revealed that in the activated conformation the above ligand molecules located in the active ligand cavities of two bivalves and a fish ER,and the stability order of the ligand binding energy was BaP>TBBPA>4-NP.The docking analysis showed that the amino acid residues of the three model ligand pockets that bind to the ligand were highly conserved.Among them,the main amino acid residues bound at the active site were Glu321,Arg362 and His492 in zebrafish,Glu290 and Arg331 in pacific oyster,and Glu242 and Arg383 in manila clam.Through this study,we proved that by exploring the cavity formed by these amino acid residues and the ligand to form an electrostatic interaction network,it is possible to determine the optimal degree of the endocrine disrupting chemicals(EDCs)to ER,and provided a theoretical basis and a technical support for the studies of endocrine disruption effects of EDCs on bivalves.

关 键 词：雌激素受体 内分泌干扰物 同源建模 分子对接 双壳类 

分 类 号：S917.4[农业科学—水产科学] Q71[生物学—分子生物学]