贝类雌激素受体的同源建模与分子对接研究

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P...

Understanding Homology Modeling and Molecular Docking of Bivalve Estrogen Receptors

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.