INTRODUCTION GPCR share a common structural feature, i.e., the presence of seven trans-membrane helices having three intracellular and three extracellular loops. The carboxyl terminal is intracellular whereas amino terminal is extracellular. Various conformational changes are observed in structure of GPCR during the binding with ligand, coupling with G protein and interaction with other proteins. In Rhodopsin class of GPCR the basic structure of GPCR is resolved by X-ray crystallography. Ligand acts as an extracellular stimulus for GPCRs to bring physiological changes in organisms. GPR139 has been found to have effective physiological role in primary dopaminergic midbrain neurons and in central nervous system. Recent reports suggested that the ligand of GPR139 protein inhibits the growth of primary dopaminergic midbrain neurons in central nervous system. These discoveries indicated the potential involvement and influence of GPR139 protein in central nervous system METHOD: Therefore, we used multi-approach analysis to investigate the role of GPR139 in the molecular mechanisms of central nervous system. In silico screening was performed to study compound 1 binding with GPR139 protein in their predicted three-dimensional structures. Compound 1 was subjected to molecular dynamics (MD) simulation and stability analysis. RESULTS The results of MD analysis suggested that the loop region in GPR139 protein structure could affect its binding with drugs. Finally, we cross-validated the predicted compound 1 through systems biology approach. Our results suggested that GPR139 might play an important role in primary dopaminergic midbrain neurons therapy.

中文翻译：

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使用分子动力学模拟和系统生物学支持的GPR139虚拟筛选，通过小分子的影响来保护原发性多巴胺能中脑神经元。

引言GPCR具有共同的结构特征，即存在七个具有三个细胞内和三个细胞外环的跨膜螺旋。羧基末端在细胞内，而氨基末端在细胞外。在与配体结合，与G蛋白偶联以及与其他蛋白相互作用的过程中，GPCR的结构发生了各种构象变化。在GPCR的视紫红质类别中，GPCR的基本结构通过X射线晶体学解析。配体充当GPCR的细胞外刺激物，使生物体发生生理变化。已发现GPR139在原发性多巴胺能中脑神经元和中枢神经系统中具有有效的生理作用。最近的报道表明，GPR139蛋白的配体抑制中枢神经系统中原发性多巴胺能中脑神经元的生长。这些发现表明GPR139蛋白在中枢神经系统中的潜在参与和影响。方法：因此，我们使用多方法分析来研究GPR139在中枢神经系统的分子机制中的作用。进行了计算机筛选，以研究化合物1与GPR139蛋白在其预测的三维结构中的结合。对化合物1进行了分子动力学（MD）模拟和稳定性分析。结果MD分析的结果表明，GPR139蛋白结构的环区可能影响其与药物的结合。最后，我们通过系统生物学方法对预测的化合物1进行了交叉验证。