G偶联蛋白受体142活性位点预测及其与激动剂对接研究  

Prediction of G-Coupled Protein Receptor 142 Active Sites and Molecular Docking with Benzoxazepine Derivative Agonists

作　　者：曹洪玉[1] 于柯楠 何佩勋 吴艳华[1] CAO Hongyu;YU Kenan;HE Peixun;WU Yanhua(College of Life Science and Technology,Dalian University,Dalian 116622,China;College of Information Engineering,Dalian University,Dalian 116622,China)

机构地区：[1]大连大学生命科学与技术学院,辽宁大连116622 [2]大连大学信息工程学院,辽宁大连116622

出　　处：《昆明理工大学学报（自然科学版）》2020年第2期92-98,共7页Journal of Kunming University of Science and Technology(Natural Science)

基　　金：国家自然科学青年基金项目(21601025);大连市高层次人才项目(2017RQ156).

摘　　要：G偶联蛋白受体142(GPR142)主要在胰岛B细胞中表达,可通过内源性配体色氨酸或合成的GPR142激动剂来调节胰岛素分泌而治疗糖尿病,是重要靶点蛋白,但因属于膜蛋白,晶体结构难以解析.本实验对GPR142膜蛋白进行同源建模,优化评估,构建出可靠的蛋白模型;根据最优蛋白三维模型预测到6个潜在药物作用活性位点并分析其氨基酸组成;将潜在药物苯并氧氮杂类衍生物对接至活性位点并分析蛋白-药物相互作用力.本实验获得可靠的GPR142蛋白模型和蛋白-药物作用模型,从而设计苯并氧氮杂类衍生物,为获得以GPR142为靶点的更高效治疗II型糖尿病的药物提供了理论基础.G-coupled protein receptor 142(GPR142),which is predominantly expressed in pancreas B cells,can adjust insulin secretion.GPR142 can be one of the key target receptor proteins for the treatment of diabetes by triggering receptor-initiated intracellular biochemical cascades with the endogenous ligand tryptophan or synthetic agonists.However,as a membrane protein,the crystal structure is hard to acquire in experiment.We generated the 3-dimentional structure of GPR142 membrane protein by homology modeling.Multiple methods were applied to optimize and evaluate the protein models for several circles.Based on the optimal protein three-dimensional model,six possible active sites were predicted and the amino acids of the sites were analyzed for revealing the potential interaction force between protein and drugs.The optimized benzoxazepine derivatives were docked into the potential active sites to obtain the protein-agonists interaction forces.These computational experiments provided reliable protein model and protein-drug interaction models,which can be used for the design of potential benzoxazepine derivative agonists of GPR142 for the treatment of type 2 diabetes.

关 键 词：G偶联蛋白受体142 同源模建 活性位点 苯并氧氮杂类衍生物 激动剂 分子对接 

分 类 号：O643.1[理学—物理化学]