多巴胺在其第三受体蛋白结构中的分子通道上传输动力学

发布时间：2018-04-12 12:18

本文选题：多巴胺 + 多巴胺受体　；参考：《物理化学学报》2017年05期

【摘要】：本文基于多巴胺与其第三受体复合蛋白(D_3R)结构,采用分子动力学技术Gromacs 4.5程序中的伞形样本方法,研究多巴胺在多巴胺第三受体蛋白结构中的运动轨迹及其过程中自由能变化,探讨多巴胺在其分子通道上传输运动机制动力学。分子模拟表明,处在发挥神经递质作用部位的多巴胺,通过D_3R结构中的功能分子通道沿着y+轴朝细胞外方向传输运动的自由能变化数值为134.6 kJ?mol~(-1),沿着y-轴朝细胞内传输运动的自由能变化为211.5 kJ?mol~(-1)。在D_3R结构中,多巴胺沿着x+、x-、z+、z-轴朝细胞双层膜方向传输运动的自由能变化分别为65.8、245.0、551.4、172.8 kJ?mol~(-1),数值说明DOP更容易沿着x+轴方向从TM5(第五跨膜螺旋)与TM6(第六跨膜螺旋)缝隙之间离开D_3R内部结构。处在细胞间隙空间的自由多巴胺,在等温等压条件下沿着逆y+轴方向通过多巴胺第三受体内功能分子通道,到达发挥神经递质作用的部位是一个自发过程,因为在该轨迹上多巴胺分子与受体相互作用是一个负自由能变化(-134.6 kJ?mol~(-1))。所以,多巴胺与多巴胺受体很容易相互结合,发挥神经递质作用。发挥了神经递质功能作用的多巴胺分子,沿着x+轴方向的保护分子通道从TM5与TM6缝隙之间离开D_3R内部结构,避免过度发挥多巴胺神经递质功能作用。根据多巴胺功能和保护分子通道观点,我们提出帕金森病新病理和精神分裂症新病理。论文还探讨多巴胺分子通道理论及其新病理应用于治疗控制这两种病症及其相关药物研究开发。
[Abstract]:Based on the structure of dopamine and its third receptor complex protein (D3R), the free energy changes of dopamine in the structure of dopamine third receptor protein were studied by using the umbrella sample method of Gromacs 4.5 program.To investigate the kinetics of dopamine transport on its molecular channels.Molecular simulations show that dopamine, which acts as a neurotransmitter,The free energy of transport along the y axis to the extracellular direction of the functional molecule channel in the D3R structure varies from 134.6 kJ / mol ~ (-1) to 211.5 kJ / mol ~ (-1) ~ 1 ~ (-1), and to 211.5 kJ / mol ~ (-1) / L ~ (-1) ~ (-1) ~ (-1) ~ 211.5 kJ / mol ~ (-1) ~ (-1) ~ (-1) ~ (-1).In the Dash3R structure,Free dopamine in intercellular space, under isothermal isobaric conditions, passing through the third functional molecular channel of dopamine through the third acceptor of dopamine in the direction of the inverse y axis, is a spontaneous process to the site where the neurotransmitter is acting.Because the dopamine molecule interacts with the receptor on this trajectory is a negative free energy variation of -134.6 kJ mol ~ (-1).Therefore, dopamine and dopamine receptors can easily bind to each other and act as neurotransmitters.The dopamine molecules which play the role of neurotransmitters, the protective molecular channels along the x-axis leave the internal structure of D3R from the gap between TM5 and TM6, so as to avoid over-exerting the function of dopamine neurotransmitters.According to dopamine function and protective molecular channel, we propose new pathology of Parkinson's disease and new pathology of schizophrenia.This paper also discusses the application of dopamine molecular channel theory and its new pathology in the treatment and control of these two diseases and the development of related drugs.
【作者单位】：云南大学化学科学与工程?药学学院自然资源药物化学教育部重点实验室;
【基金】：国家自然科学基金(21163024,21563032)资助项目~~
【分类号】：O643.1;R749.3

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