论文部分内容阅读
多巴胺是大脑中含量最丰富的儿茶酚胺类神经递质,主要通过多巴胺受体调控中枢神经系统的多种生理功能,其中多巴胺D2受体与药物成瘾、精神分裂症、帕金森病等多种疾病的发生相关。然而多巴胺D2受体的晶体结构至今尚未解析出来,给相关疾病的药物设计与开发带来困难。本文采用同源模建的方法,用目前与多巴胺D2受体同源性最高的多巴胺D3受体(3PBL)作为模板,构建多巴胺D2受体的三维结构。经过优化和分子动力学模拟,用Profile-3D和Ramachandran plot对模型进行评估,然后用多巴胺D2受体拮抗剂千金藤啶碱(stepholidine,SPD)进行对接验证,证明构建的多巴胺D2受体模型合理、可靠。
Dopamine is the most abundant catecholaminergic neurotransmitter in the brain, which regulates many physiological functions of the central nervous system mainly through dopamine receptors. Among them, dopamine D2 receptor and drug addiction, schizophrenia, Parkinson’s disease and other diseases Related to the occurrence of. However, the crystal structure of dopamine D2 receptor has not been resolved so far, which brings difficulties to drug design and development of related diseases. In this paper, the three-dimensional structure of dopamine D2 receptor was constructed by homologous modeling and using dopamine D3 receptor (3PBL) which is the most homologous to D2 receptor of dopamine as a template. After optimization and molecular dynamics simulations, the model was evaluated with Profile-3D and Ramachandran plot and then validated by docking with dopamine D2 receptor antagonist stepholidine (SPD), demonstrating that the constructed dopamine D2 receptor model is reasonable ,reliable.