物理化学学报2017，Vol.33Issue(5)：927-940,14.DOI:10.3866/PKU.WHXB201702211
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
Molecular Dynamics of Dopamine to Transmit through Molecular Channels within D3R
摘要
Abstract
In this paper,based on the complex protein structure of third dopamine receptor (D3R) with dopamine (DOP),we have studied the trajectories with the free energy changes of D3R for DOP to move along its molecular channels and then probed the molecular dynamics mechanism of DOP transmitting along molecular channels,using molecular dynamics techniques including the potential mean force (PMF) of umbrella samplings from the GROMACS program (version 4.5).Simulation results show that for DOP located in the space region of D3R to act as a neurotransmitter transmitting toward the outside of cell,the free energy change is 134.6 kJ· mol-1 along the functional molecular channel of y+ axis within D3R,and 211.5 k J· mol 1 along the y-axis towards the intracellular part.Within the structure of D3R,the free energy changes are 65.8,245.0,551.4,172.8 kJ· mo1-1 for DOP to transmit along the x+,x-,z+,z-axes,respectively,towards cell bilayer membrane,indicating that DOP leaves more easily along the x+ axis through the gap between TM5 (the fifth transmembrane helix) and TM6 (the sixth transmembrane helix) from the internal structure of D3R.When free DOP molecules are located in the intercellular spaces,once they start moving along the inverse y+ axis direction under constant pressure and temperature,they spontaneously pass through the functional molecular channel to reach the space region of D3R to act as a neurotransmitter,because the free energy change between DOP and D3R along the inverse y+ axis direction is negative (134.6 kJ· mol-1).Therefore,DOP interacting with D3R can easily play the role of a neurotransmitter.After DOP molecules have performed the actions of a neurotransmitter,they leave the internal structure of D3R along the x+ axis of a protective molecular channel through the gap between TM5 and TM6 to avoid excessive function as transmitter.According to dopamine functional and protective molecular channels,we suggest new pathologies and the finding and development of new drugs for Parkinson's disease and schizophrenia.关键词
多巴胺/多巴胺受体/分子通道/分子模拟/帕金森病/精神分裂症Key words
Dopamine/Dopamine receptor/Molecular channel/Molecular simulation/Parkinson's disease/Schizophrenia分类
化学化工引用本文复制引用
李爱静,谢炜,王明,徐四川..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[J].物理化学学报,2017,33(5):927-940,14.基金项目
The project was supported from the National Natural Science Foundation of China (21163024,21563032).国家自然科学基金(21163024,21563032)资助项目 （21163024,21563032）
