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

doi:10.3866/PKU.WHXB201702211

Abstract

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 kJ·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·mol^-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.

Key words: Dopamine, Dopamine receptor, Molecular channel, Molecular simulation, Parkinson's disease, Schizophrenia

MSC2000:

O641

Ai-Jing LI,Wei XIE,Ming WANG,Si-Chuan XU. Molecular Dynamics of Dopamine to Transmit through Molecular Channels within D₃R[J].Acta Phys. -Chim. Sin., 2017, 33(5): 927-940.

References

1	Carlsson A. ; Waters N. ; Waters S. ; Carlsson M. L. Brain Res. 2000, 31, 342.
2	Li F. ; Shu S. Y. ; Bao X. M. Neurosci. Bull 2003, 19 (6), 405.
2	李凡; 舒斯云; 包新民. 神经科学通报, 2003, 19 (6), 405.
3	Suri R. E. ; Bargas J. ; Arbib M. A. Neuroscience 2001, 103, 65.
4	Salum C. ; Roque S. A. ; Pickering A. Neurocomputing 1999, 26- 27, 845.
5	Bian, F. Y.; Shi, G. J.; Chi, S. M.; Xu, S. C. The Perspective Insight into the Pathology of Parkinsonism Using the Molecular Channel Theory of Dopamine inside its Receptor Membrane Protein. Chinese Chemical Society at the Second National Conference on Bio-physical Chemistry (NCBPC2) and the International Forum on Development of Chinese Bio-Physical Chemistry, Wuhan University, Wuhan, China, Oct 15-18, 2012.
6	Xu, S. C.; Shi, G. J.; Chi, S. M. The Active Site Residues and the Molecular Channels for Dopamine within D3R Membrane Protein. The 28thCCS (Chinese Chemical Society) Congress, Sichuan University, Chengdu, China, April 13-16, 2012.
7	Kebabian J. W. ; Calne D. B. Nature 1979, 277 (5692), 93.
8	Bunzow J. R. ; Van Tol H. H. M. ; Grandy D. K. ; Albert P. ; Salon J. ; Christie M. Nature 1988, 336, 783.
9	Dearry A. ; Gingrich J. A. ; Falardeau P. ; Fremeau R. T. ; Bates M. D. ; Caron M. G. Nature 1990, 347, 72.
10	Sokoloff P. ; Giros B. ; Martres M. P. ; Bouthenet M. L. ; Schwartz J. C. Nature 1990, 347, 146.
11	Van Tol H. H. ; Bunzow J. R. ; Guan H. C. ; Sunahara R. K. ; Seeman P. ; Niznik H. B. ; Civelli O. Nature 1991, 350, 610.
12	Sunahara R. K. ; Guan H. C. ; O′Dowd B. F. ; Seeman P. ; Laurier L. G. ; Ng G. ; George S. R. ; Torchia J. ; Van Tol H. H. ; Niznik H. B. Nature 1991, 350, 614.
13	Chien E. Y. T. ; Liu W. ; Zhao Q. ; Katritch V. ; Han G. W. ; Hanson M. A. ; Shi L. ; Newman A. H. ; Javitch J. A. ; Cherezov V. ; Stevens R. C. Science 2010, 330, 1091.
14	Jin Y. ; Wang Y. ; Bian F. Y. ; Shi Q. ; Ge M. F. ; Wang S. ; Zhang X. K. ; Xu S. C. Acta Phys.-Chim. Sin 2011, 27 (10), 2432.
14	金毅; 王悦; 卞富永; 史强; 葛茂发; 王树; 张兴康; 徐四川. 物理化学学报, 2011, 27 (10), 2432.
15	Xu S. C. ; De ng ; S R. ; Ma L. Y. ; Shi Q. ; Ge M. F. ; Zhang X. K. Acta Phys.-Chim. Sin. 2009, 25, 1290.
15	徐四川; 邓圣荣; 马丽英; 史强; 葛茂发; 张兴康. 物理化学学报, 2009, 25, 1290.
16	Hoff B. ; Strandberg E. ; Ulrich A. S. ; Tieleman D. P. ; Posten C. Biophys. J. 2005, 88, 1818.
17	Janosi L. ; Gorfe A. A. J. Chem. Theory Comput. 2010, 6, 3267.
18	Su Z. Y. ; Wang Y. T. J. Phys. Chem. B 2011, 115, 796.
19	Merlino A. ; Vitiello G. ; Grimaldi M. ; Sica F. ; Busi E. ; Basosi R. ; D′Ursi A. M. ; Fragneto G. ; Paduano L. ; D′Errico G. J. Phys. Chem. B 2012, 116, 401.
20	Polyansky A. A. ; Volynsky P. E. ; Nolde D. E. ; Arseniev A. S. ; Efremov R. G. J. Phys. Chem. B 2005, 109, 15052.
21	Puri A. ; Jang H. ; Yavlovich A. ; Masood M. A. ; Veenstra T. D. ; Luna C. ; Aranda-Espinoza H. ; Nussinov R. ; Blumenthal R. Langmuir 2011, 27, 15120.
22	Payandeh J. ; Gamal El-Din T. M. ; Scheuer T. ; Zheng N. ; Catterall W. A. Nature 2012, 486, 135.
23	J?nsson P. ; Jonsson M. P. ; H??k F. Nano Lett. 2010, 10, 1900.
24	Marrink S. J. ; Lindahl E. ; Edholm O. ; Mark A. E. J. Am. Chem. Soc. 2001, 123, 8638.
25	Miyamoto S. ; Kollman P. A. J. Comput. Chem. 1992, 13, 952.
26	Berendsen H. J. C. ; van der Spoel D. ; van Drunen R. Comput. Phys. Commun. 1995, 91, 43.
27	Van der Spoel D. ; Lindahl E. ; Hess B. ; Groenhof G. ; Mark A. E. ; Berendsen H. J. C. J. Comput. Chem. 2005, 26, 1701.
28	Van der Spoel, D.; Lindahl, E.; Hess, B.; van Buuren, A. R.; Apol, E.; Meulenhoff, P. J.; Berendsen, H. J. Gromacs User Manual, version 4.5; www.gromacs.org.
29	Humphrey W. ; Dalke A. ; Schulten K. J. Mol. Graph. Model. 1996, 14, 33.
30	Daura X. ; Mark A. E. ; Van Gunsteren W. F. J. Comput. Chem. 1998, 19 (5), 535.
31	Van Gunsteren, W.; Billeter, S.; Eising, A.; Hunenberger, P.; Kruger, P.; Mark, A.; Tironi, I. Biomolecular Simulation: the Gromos 96 Manual and User Guide, 1st ed.; Hochschulverlag AG an der ETH Zurich: Zurich, Switzerland, 1996.
32	Bian F. Y. ; Zhang J. W. ; Wang D. ; Xu S. C. Acta Phys.-Chim. Sin. 2014, 30, 1947.
32	卞富永; 张继伟; 王丹; 徐四川. 物理化学学报, 2014, 30, 1947.
33	Zhang J.W. ; Bian F. Y. ; Shi G. J. ; Xu S. C. Acta Phys.-Chim. Sin. 2014, 30, 183.
33	张继伟; 卞富永; 施国军; 徐四川. 物理化学学报, 2014, 30, 183.
34	Hess B. ; Kutzner C. ; van der Spoel D. ; Lindahl E. J. Chem. Theory Comput. 2008, 4, 435.
35	Wang M. ; Xie W. ; Li A. J. ; Xu S. C. Chirality 2016, 28 (10), 674- 685.
36	Xie W. ; Wang M. ; Li A.J. ; Xu S. C. J. Biomol. Struct. Dyn. 2016.
37	Xie W. ; Xu Z. R. ; Wang M. ; Xu S. C. Acta Phys.-Chim. Sin. 2016, 32, 907.
37	谢炜; 徐泽人; 王明; 徐四川. 物理化学学报, 2016, 32, 907.
38	Shi G. J. ; Wang Y. ; Jin Y. ; Chi S. M. ; Shi Q. ; Ge M. F. ; Zhang X. K. ; Xu S. C. J. Biomol. Struct. Dyn. 2012, 30 (5), 559.
39	Xu S. C. ; Chi S. M. ; Jin Y. ; Shi Q. ; Ge M. F. ; Wang S. ; Zhang X. K. J. Mole. Model. 2012, 18 (1), 377.
40	Chi S. ; Xie W. ; Zhang J. ; Xu S. C. J. Biomol. Struct. Dyn. 2015, 33 (10), 2234.
41	Hub J. S. ; de Groot B. L. ; van der Spoel D. J. Chem. Theory Comput. 2010, 6, 3713.
42	Marrink S. J. ; Berendsen H. J. C. J. Phys. Chem. 1994, 98, 4155.
43	Marrink S. J. ; Jaehnig F. ; Berendsen H. J. C. Biophys. J. 1996, 71, 632.
44	Zahn D. ; Brickmann J. Chem. Phys. Lett. 2002, 352, 441.
45	Bemporad D. ; Essex J. W. ; Luttmann C. J. Phys. Chem. B 2004, 108, 4875.
46	Shinoda W. ; Mikami M. ; Baba T. ; Hato M. J. Phys. Chem. B 2004, 108, 9346.
47	Nichols J. W. ; Deamer D. W. Proc. Nat. Acad. Sci. U. S. A. 1980, 77, 2038.
48	Benga G. ; Pop V. I. ; Popescu O. ; Borza V. J. Biochem. Bioph. Meth. 1990, 21, 87.
49	Jansen M. ; Blume A. Biophys. J. 1995, 68, 997.
50	Andrasko J. ; Forsén S. Biochem. Biophys. Res. Commun. 1974, 60, 813.
51	Graziani Y. ; Livne A. J. Membr. Biol. 1972, 7, 275.
52	Khavrutskii I. V. ; Gorfe A. A. ; Lu B. ; McCammon J. A. J. Am. Chem. Soc. 2009, 131, 1706.
53	Papahadjopoulos D. ; Nir S. ; Ohki S. Biochim. Biophys. Acta 1972, 266, 561.
54	Boateng C. A. ; Bakare O. M. ; Zhan J. ; Banala A. K. ; Burzynski C. ; Pommier E. ; Keck T. M. ; Donthamsetti P. ; Javitch J. A. ; Rais R. ; Slusher B. S. ; Xi Z. X. ; Newman A. H. J. Med. Chem. 2015, 58, 6195.
55	Peelaerts W. ; Bousset L. ; Van der Perren A. ; Moskalyuk A. ; Pulizzi R. ; Giugliano M. ; Van den Haute C. ; Melki R. ; Baekelandt V. Nature 2005, 522, 340.
56	Su W. ; Chen H. B. ; Li S. H. ; Wu D. Y. J. Gen. Pract. 2008, 7, 683.
56	苏闻; 陈海波; 李淑华; 吴冬颖. 中华全科医师杂志, 2008, 7, 683.

[1]	Changsheng Zhang,Luhua Lai. Physiochemical Mechanisms of Biomolecular Liquid-Liquid Phase Separation [J]. Acta Physico-Chimica Sinica, 2020, 36(1): 1907053-0.
[2]	Di YIN,Zongyang QIU,Pai LI,Zhenyu LI. A Molecular Dynamics Study of Carbon Dimerization on Cu(111) Surface with Optimized DFTB Parameters [J]. Acta Phys. -Chim. Sin., 2018, 34(10): 1116-1123.
[3]	Yi WANG,Nan-Fang JIA,Sheng-Li QI,Guo-Feng TIAN,De-Zhen WU. Synthesis, Characterization and Memory Performance of Naphthalimides Containing Various Electron-Withdrawing Moieties [J]. Acta Phys. -Chim. Sin., 2017, 33(11): 2227-2236.
[4]	Xiao-Long LIU,Xiao-Xia LI,Song HAN,Xian-Jie QIAO,Bei-Jing ZHONG,Li GUO. Initial Reaction Mechanism of RP-3 High Temperature Oxidation Simulated with ReaxFF MD [J]. Acta Phys. -Chim. Sin., 2016, 32(6): 1424-1433.
[5]	Da-Chao CUI,Wei-Tong REN,Wen-Fei LI,Wei WANG. Metadynamics Simulations of Mg²⁺ Transfer in the Late Stage of the Adenylate Kinase Catalytic Cycle [J]. Acta Phys. -Chim. Sin., 2016, 32(2): 429-435.
[6]	Shi-Wen XU,Dong-Qiang LIN,Shan-Jing YAO. Molecular Simulations on Dynamic Binding of Ibuprofen onto Site II of Human Serum Albumin: One Potential Way Analysis [J]. Acta Phys. -Chim. Sin., 2016, 32(11): 2811-2818.
[7]	Xiang LU,Xun CHEN,Ya-Shun WANG,Yuan-Yuan TAN,Zi-Yuan GAOMU. Molecular Dynamics Simulation of Gas Transport in Amorphous Polyisoprene [J]. Acta Phys. -Chim. Sin., 2016, 32(10): 2523-2530.
[8]	Meng-Yao. ZHAO,Xue-Ping. YANG,Xiao-Ning. YANG. Molecular Dynamics Simulation of Water Molecules in Confined Slit Pores of Graphene [J]. Acta Phys. -Chim. Sin., 2015, 31(8): 1489-1498.
[9]	YANG Shuo, XU Gui-Yin, HAN Jin-Peng, BING Huan, DOU Hui, ZHANG Xiao-Gang. Nitrogen-Doped Porous Carbon Derived from Dopamine-Modified Polypyrrole and Its Electrochemical Capacitive Behavior [J]. Acta Phys. -Chim. Sin., 2015, 31(4): 685-692.
[10]	WU Xuan-Jun, ZHAO Peng, FANG Ji-Min, WANG Jie, LIU Bao-Shun, CAI Wei-Quan. Simulation on the Hydrogen Storage Properties of New Doping Porous Aromatic Frameworks [J]. Acta Phys. -Chim. Sin., 2014, 30(11): 2043-2054.
[11]	BIAN Fu-Yong, ZHANG Ji-Wei, WANG Dan, XU Si-Chuan. Molecular Dynamics Simulation of the Permeation of Methyldopa through POPC Phospholipid Bilayer Membrane [J]. Acta Phys. -Chim. Sin., 2014, 30(10): 1947-1956.
[12]	ZHANG Ji-Wei, BIAN Fu-Yong, SHI Guo-Jun, XU Si-Chuan. Molecular Dynamics Simulation of Dopamine Diffusion within and Permeation through POPC Phospholipid Bilayer Membrane [J]. Acta Phys. -Chim. Sin., 2014, 30(1): 183-193.
[13]	HUANG Yong-Qi, KANG Xue, XIA Bing, LIU Zhi-Rong. Mechanism of 3D Domain Swapping for M^pro-C: Clues from Molecular Simulations [J]. Acta Phys. -Chim. Sin., 2012, 28(10): 2411-2417.
[14]	MEI Yong-Jun, HAN Yi-Xiu, ZHOU Hong, YAO Lin, JIANG Bo. Synergism between Hydrophobically Modified Polyacrylic Acid and Wormlike Micelles [J]. Acta Phys. -Chim. Sin., 2012, 28(07): 1751-1756.
[15]	SUN De-Lin, ZHOU Jian. Dissipative Particle Dynamics Simulations on Mesoscopic Structures of Nafion and PVA/Nafion Blend Membranes [J]. Acta Phys. -Chim. Sin., 2012, 28(04): 909-916.

Molecular Dynamics of Dopamine to Transmit through Molecular Channels within D₃R

RichHTML

PDF

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Comments

Recommended 0

Molecular Dynamics of Dopamine to Transmit through Molecular Channels within D3R

RichHTML

PDF

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Comments

Recommended 0

Molecular Dynamics of Dopamine to Transmit through Molecular Channels within D₃R