Citation: 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 Physico-Chimica Sinica, ;2014, 30(10): 1947-1956. doi: 10.3866/PKU.WHXB201408271 shu

Molecular Dynamics Simulation of the Permeation of Methyldopa through POPC Phospholipid Bilayer Membrane

1.
1. Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. China;
2. Chuxiong Medical College, Chuxiong 675005, Yunnan Province, P. R. China

Received Date: 13 May 2014
Available Online: 27 August 2014
Fund Project:

The molecular dynamics mechanism for methyldopa permeation through the phospholipid bilayer membrane has been studied by molecular dynamics simulation. The phospholipid bilayer membrane used in the work was one type of lecithin phospholipid bilayer membrane called the 1-palmitoyl-2-oleoyl-glycero-3- phosphate dylcholine (POPC) bilayer membrane, and the molecular dynamics simulation was performed with the Gromacs program. The free energy barrier for methyldopa to permeate through the POPC bilayer membrane was 99.9 kJ·mol^-1 (310 K) from the molecular dynamics simulation, suggesting that methyldopa is capable of permeating through the cell membrane. The free energy barrier for methyldopa to diffuse through the POPC bilayer membrane was 16.9-27.7 kJ·mol^-1 (310 K), which indicates that it is easy for methyldopa to diffuse through the cell membrane. Therefore, the results of the free energy barrier give information of the mechanism for methyldopa to metabolize in the human body. Furthermore, the results help to understand the mechanism for methyldopa in treating hypertension disease, and have significance for developing new drugs to control hypertension.
- Methyldopa,
- Hypertension,
- Cell membrane,
- POPC,
- Molecular simulation,
- Molecular dynamics
1. [1]
  
  (1) Swift, P. A.; Macgre r, G. A. Journal of Renin-Angiotensin-Aldosterone System 2002, 3, 103. doi: 10.3317/jraas.2002.010
2. [2]
  (2) Chobanian, A. V.; Bakris, G. L.; Black, H. R.; Cushman,W. C.; Green, L. A.; Izzo, J. L.; Jones, D.W.; Materson, B. J.; Oparil, S.;Wright, J. T.; Roccella, E. J. Hypertension 2003, 42, 1206. doi: 10.1161/01.HYP.0000107251.49515.c2
3. [3]
  (3) Vedin, J. A.;Wilhelmsson, C. E.Werko, L. Brit. Heart J. 1973, 35, 1285. doi: 10.1136/hrt.35.12.1285
4. [4]
  (4) Dollery, C. T.; Harington, M.; Hodge, J. V. Brit. Heart J. 1963, 25, 670. doi: 10.1136/hrt.25.5.670
5. [5]
  (5) Bosworth, H. B.; Olsen, M. K.; Oddone, E. Z. Am. Heart. J. 2005, 149 (5), 795. (6) Arauz-Pacheco, C.; Parrott, M. A.; Raskin, P. Diabetes Care 2002, 25, 134. doi: 10.2337/diacare.25.1.134
6. [6]
  (7) Lant, A. Drugs 1986, 31 (4), 40. (8) Bissoli, N. S.; Vasqufz, E. C.; Cabral, A. M. Pharmacol. Res. 1996, 33, 47. doi: 10.1006/phrs.1996.0008
7. [7]
  (9) Warram, J. H.; Laffel, L. M.; Valsania, P.; Christlieb, A. R.; Krolewski, A. S. Arch Intern. Med. 1991, 151 (7), 1350. doi: 10.1001/archinte.1991.00400070114014
8. [8]
  (10) Langer, S. Z.; Cavero, I.; Massingham, R. Hypertension 1980, 2, 372. doi: 10.1161/01.HYP.2.4.372
9. [9]
  (11) Pollare, T.; Sithell, H.; Selnius, J.; Berne, C. Diabetologia 1988, 31, 415. doi: 10.1007/BF00271585
10. [10]
  (12) Hansson, L.; Lindhol, L. H.; Niskanen, L.; Lanke, J.; Hedner, T.; Niklason, A.; Luomanmaki, K.; Dahlof, B.; de Faire, U.; Molin, C.; Karlberg, B.;Wester, P. O.; Bjorck, J. E. Lancet 1999, 353, 611. doi: 10.1016/S0140-6736(98)05012-0
11. [11]
  (13) Brown, M. J.; Palmer, C. R.; Castaigne, A.; de Leeuw, P.W.; Mancia, G.; Rosenthal, T.; Ruilope, L. M. Lancet 2000, 356, 366. doi: 10.1016/S0140-6736(00)02527-7
12. [12]
  (14) Hansson, L.; Hedner, T.; Lund-Johansen, P.; Kjeldsen, S. E.; Lindholm, L. H.; Syvertsen, J. O.; Lanke, J.; de Faire, U.; Dahlof, B.; Karlberg, B. Lancet 2000, 356, 359. doi: 10.1016/S0140-6736(00)02526-5
13. [13]
  (15) Lagunin, A. A.; mazkov, O. A.; Filimonov, D. A.; Gureeva, T. A.; Dilakyan, E. A.; Kugaevskaya, E. V.; Elisseeva, Y. E.; Solovyeva, N. I.; Poroikov, V. V. J. Med. Chem. 2003, 46, 3326. doi: 10.1021/jm021089h
14. [14]
  (16) Ferrari, R.; Ceconi, C.; Curello, S.; Pepi, P.; Mazzoletti, A.; Visioli, O. Cardiovasc. Drugs. Ther. 1996, 10, 639. doi: 10.1007/BF00052511
15. [15]
  (17) Luke, R. G.; Kennedy, A. C. Br. Med. J. 1964, 4 (1), 27. (18) Johnson, P.; Kitchin, A. H.; Lowther, C. P.; Turner, R.W. Br. Med. J. 1966, 1, 133. doi: 10.1136/bmj.1.5480.133
16. [16]
  (19) Iliodromiti, S.; Mackenzie, F.; Lindsay, R. S. Drug Notes 2010, 27 (4), 166. (20) Mancia, G.; Ferrai, A.; Gre rin, L. J. Am. Cardiol. 1980, 46(5), 1237. (21) Webster, J.; Jeffers, T. A.; Galloway, D. B.; Petrie, J. C.; Barker, N. P. Br. Med. J. 1977, 8 (1), 76. (22) Bobik, A.; Jennings, G.; Jackman, G.; Oddie, C.; Korner, P. Hypertension 1986, 8, 16. doi: 10.1161/01.HYP.8.1.16
17. [17]
  (23) Freed, C. R.;Wang, C. H.; U2Prichcrd, D. C.Hypertension 1984, 6, II34. (24) Robertson, D.; Tung, C. S.; ldberg, M. R.; Hollister, A. S.; Gerkens, J. F.; Oates, J. A. Hypertension 1984, 6, 45. (25) Korner, P. I.; Head, G. A.; Bobik, A.; Badoer, E.; Aberdeen, J. A. Hypertension 1984, 6, 63. (26) Marrink, S. J.; Berendsen, H. J. C. J. Phys. Chem. 1994, 98, 4155. doi: 10.1021/j100066a040
18. [18]
  (27) Marrink, S. J.; Jaehnig, F.; Berendsen, H. J. C. Biophys. J. 1996, 71, 632. doi: 10.1016/S0006-3495(96)79264-0
19. [19]
  (28) Zahn, D.; Brickmann, J. Chem. Phys. Lett. 2002, 352, 441. doi: 10.1016/S0009-2614(01)01437-3
20. [20]
  (29) Bemporad, D.; Essex, J.W.; Luttmann, C. J. Phys. Chem. B 2004, 108, 4875. doi: 10.1021/jp035260s
21. [21]
  (30) Shinoda,W.; Mikami, M.; Baba, T.; Hato, M. J. Phys. Chem. B 2004, 108, 9346. doi: 10.1021/jp035998+
22. [22]
  (31) Nichols, J.W.; Deamer, D.W. Proc. Nat. Acad. Sci. U. S. A. 1980, 77, 2038. doi: 10.1073/pnas.77.4.2038
23. [23]
  (32) Benga, G.; Pop, V. I.; Popescu, O.; Borza, V. J. Biochem. Biophys. Methods 1990, 21, 87. doi: 10.1016/0165-022X(90)90057-J
24. [24]
  (33) Jansen, M.; Blume, A. Biophys. J. 1995, 68, 997. doi: 10.1016/S0006-3495(95)80275-4
25. [25]
  (34) Andrasko, J.; Forsén, S. Biochem. Biophys. Res. Commun. 1974, 60, 813. doi: 10.1016/0006-291X(74)90313-1
26. [26]
  (35) Graziani, Y.; Livne, A. J. Membr. Biol. 1972, 7, 275. doi: 10.1007/BF01867920
27. [27]
  (36) Khavrutskii, I. V.; rfe, A. A.; Lu, B.; McCammon, J. A. J. Am. Chem. Soc. 2009, 131, 1706. doi: 10.1021/ja8081704
28. [28]
  (37) Papahadjopoulos, D.; Nir, S.; Ohki, S. Biochim. Biophys. Acta 1972, 266, 561. doi: 10.1016/0005-2736(72)90354-9
29. [29]
  (38) Zhang, J.W.; Bian, F. Y.; Shi, G. J.; Xu, S. C. Acta Phys. -Chim. Sin. 2014, 30 (1), 183. [张继伟, 卞福永, 施国军, 徐四川. 物理化学学报, 2014, 30 (1), 183.] doi: 10.3866/PKU.WHXB201311281
30. [30]
  (39) Yang, F. Y. Biological Cell; Science Press: Beijing, 2005. [杨福愉. 生物膜. 北京: 科学出版社, 2005.] (40) Hoff, B.; Strandberg, E.; Ulrich, A. S.; Tieleman, D. P.; Posten, C. Biophys. J. 2005, 88, 1818. doi: 10.1529/biophysj.104.052399
31. [31]
  (41) Janosi, L.; rfe, A. A. J. Chem. Theory Comput. 2010, 6, 3267. doi: 10.1021/ct100381g
32. [32]
  (42) Su, Z. Y.;Wang, Y. T. J. Phys. Chem. B 2011, 115, 796. doi: 10.1021/jp107599v
33. [33]
  (43) Dunkin, C. M.; Pokorny, A.; Almeida, P. F.; Lee, H. S. J. Phys. Chem. B 2011, 115, 1188. doi: 10.1021/jp107763b
34. [34]
  (44) Chen, R.; Poger, D.; Mark, A. E. J. Phys. Chem. B 2011, 115, 1038. doi: 10.1021/jp110002q
35. [35]
  (45) 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. doi: 10.1021/jp204781a
36. [36]
  (46) Yamamoto, E.; Akimoto, T.; Shimizu, H.; Hirano, Y.; Yasui, M.; Yasuoka, K. J. Phys. Chem. B 2012, 116, 8989. (47) Polyansky, A. A.; Volynsky, P. E.; Nolde, D. E.; Arseniev, A. S.; Efremov, R. G. J. Phys. Chem. B 2005, 109, 15052. doi: 10.1021/jp0510185
37. [37]
  (48) 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. doi: 10.1021/la203453x
38. [38]
  (49) Manna, M.; Mukhopadhyay, C. Langmuir 2009, 25, 12235. doi: 10.1021/la902660q
39. [39]
  (50) Hartshorn, M.; Jewett, C. M.; Brozik, J. A. Langmuir 2010, 26, 2609. doi: 10.1021/la904308g
40. [40]
  (51) Mondal, S.; Mukhopadhyay, C. Langmuir 2008, 24, 10298. doi: 10.1021/la8015589
41. [41]
  (52) Soemo, A. R.;Wirth, M. J. Langmuir 2010, 26, 2196. doi: 10.1021/la9038914
42. [42]
  (53) Payandeh, J.; Gamal El-Din, T. M.; Scheuer, T.; Zheng, N.; Catterall,W. A. Nature 2012, 486, 135. (54) Jönsson, P.; Jonsson, M. P.; Höök, F. Nano Lett. 2010, 10, 1900. doi: 10.1021/nl100779k
43. [43]
  (55) Carr, R.;Weinstock, I. A.; Sivaprasadarao, A.; Müller, A.; Aksimentiev, A. Nano Lett. 2008, 8, 3916. doi: 10.1021/nl802366k
44. [44]
  (56) Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren,W. F.; Hermans, J.; Pullman, B. J. Am. Chem. Soc. 2001, 123, 8638. doi: 10.1021/ja0159618
45. [45]
  (57) Miyamoto, S.; Kollman, P. A. J. Comput. Chem. 1992, 13, 952. (58) Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. J. Chem. Theory Comput. 2008, 4, 435. doi: 10.1021/ct700301q
46. [46]
  (59) Van der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark, A. E.; Berendsen, H. J. C. J. Comput. Chem. 2005, 26, 1701. (60) Berendsen, H. J. C.; van der Spoel, D.; van Drunen, R. Comp. Phys. Commun. 1995, 91, 43. doi: 10.1016/0010-4655(95)00042-E
47. [47]
  (61) Frisch, M. J.; Trucks, G.W.; Schlegel, H. B.; et al. Gaussian 03, Revision E.01; Gaussian Inc.:Wallingford, CT, 2004. (62) Schuettelkopf, A.W.; van Aalten, D. M. F. Acta Crystallogr. 2004, D60, 1355. (63) Wang, Y.; Bian, F.; Deng, S. R.; Shi, Q.; Ge, M. F.;Wang, S.; Zhang, X. K.; Xu, S. C. Journal of Biomolecular Structure & Dynamics 2011, 28, 881. doi: 10.1080/07391102.2011.10508615
48. [48]
  (64) Xu, S. C.; Chi, S. M.; Jin, Y.; Shi, Q.; Ge, M. F.;Wang, S.; Zhang, X. K. J. Mol. Model. 2012, 18, 377. doi: 10.1007/s00894-011-1083-7
49. [49]
  (65) Humphrey,W.; Dalke, A.; Schulten, K. J. Mol. Graph. 1996, 14, 33. doi: 10.1016/0263-7855(96)00018-5
50. [50]
  (66) Hess, B.; Bekker, H.; Berendsen, H. J. C.; Fraaije, J. G. E. M. J. Comput. Chem. 1997, 18, 1463. (67) Darden, T.; York, D.; Pedersen, L. J. Chem. Phys. 1993, 98, 10089. doi: 10.1063/1.464397
51. [51]
  (68) Essman, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. J. Chem. Phys. 1995, 103, 8577. doi: 10.1063/1.470117
52. [52]
  (69) Berendsen, H. J. C.; Postma, J. P. M.; Gunsteren,W. F.; Dinola, A.; Haak, J. R. J. Chem. Phys. 1984, 81, 3684. doi: 10.1063/1.448118
53. [53]
  (70) Hub, J. S.; de Groot, B. L.; van der Spoel, D. J. Chem. Theory Comput. 2010, 6, 3713. doi: 10.1021/ct100494z
54. [54]
  (71) Chiu, S.W.; Subramaniam, S.; Jakobsson, E. Biophys. J. 1999, 76, 1939. doi: 10.1016/S0006-3495(99)77353-4
55. [55]
  (72) Erdtman, E.; dos Santos, D. J. V. A.; LÖfgren, L.; Eriksson, L. A. Chem. Phys. Lett. 2008, 463, 178. doi: 10.1016/j.cplett.2008.08.021
56. [56]
  (73) Bauer, B. A.; Lucas, T. R.; Meninger, D. J.; Patel, S. Chem. Phys. Lett. 2011, 508, 289. doi: 10.1016/j.cplett.2011.04.052
1. [1]
  Feng Zheng , Ruxun Yuan , Xiaogang Wang . “Research-Oriented” Comprehensive Experimental Design in Polymer Chemistry: the Case of Polyimide Aerogels. University Chemistry, 2024, 39(10): 210-218. doi: 10.12461/PKU.DXHX202404027
2. [2]
  Shule Liu . Application of SPC/E Water Model in Molecular Dynamics Teaching Experiments. University Chemistry, 2024, 39(4): 338-342. doi: 10.3866/PKU.DXHX202310029
3. [3]
  Xiaochen Zhang , Fei Yu , Jie Ma . 多角度数理模拟在电容去离子中的前沿应用. Acta Physico-Chimica Sinica, 2024, 40(11): 2311026-. doi: 10.3866/PKU.WHXB202311026
4. [4]
  Pingping Zhu , Yongjun Xie , Yuanping Yi , Yu Huang , Qiang Zhou , Shiyan Xiao , Haiyang Yang , Pingsheng He . Excavation and Extraction of Ideological and Political Elements for the Virtual Simulation Experiments at Molecular Level: Taking the Project “the Simulation and Computation of Conformation, Morphology and Dimensions of Polymer Chains” as an Example. University Chemistry, 2024, 39(2): 83-88. doi: 10.3866/PKU.DXHX202309063
5. [5]
  Yaling Chen . Basic Theory and Competitive Exam Analysis of Dynamic Isotope Effect. University Chemistry, 2024, 39(8): 403-410. doi: 10.3866/PKU.DXHX202311093
6. [6]
  Jinfu Ma , Hui Lu , Jiandong Wu , Zhongli Zou . Teaching Design of Electrochemical Principles Course Based on “Cognitive Laws”: Kinetics of Electron Transfer Steps. University Chemistry, 2024, 39(3): 174-177. doi: 10.3866/PKU.DXHX202309052
7. [7]
  Yeyun Zhang , Ling Fan , Yanmei Wang , Zhenfeng Shang . Development and Application of Kinetic Reaction Flasks in Physical Chemistry Experimental Teaching. University Chemistry, 2024, 39(4): 100-106. doi: 10.3866/PKU.DXHX202308044
8. [8]
  Xuzhen Wang , Xinkui Wang , Dongxu Tian , Wei Liu . Enhancing the Comprehensive Quality and Innovation Abilities of Graduate Students through a “Student-Centered, Dual Integration and Dual Drive” Teaching Model: A Case Study in the Course of Chemical Reaction Kinetics. University Chemistry, 2024, 39(6): 160-165. doi: 10.3866/PKU.DXHX202401074
9. [9]
  Dexin Tan , Limin Liang , Baoyi Lv , Huiwen Guan , Haicheng Chen , Yanli Wang . Exploring Reverse Teaching Practices in Physical Chemistry Experiment Courses: A Case Study on Chemical Reaction Kinetics. University Chemistry, 2024, 39(11): 79-86. doi: 10.12461/PKU.DXHX202403048
10. [10]
  Yiying Yang , Dongju Zhang . Elucidating the Concepts of Thermodynamic Control and Kinetic Control in Chemical Reactions through Theoretical Chemistry Calculations: A Computational Chemistry Experiment on the Diels-Alder Reaction. University Chemistry, 2024, 39(3): 327-335. doi: 10.3866/PKU.DXHX202309074
11. [11]
  Yue Wu , Jun Li , Bo Zhang , Yan Yang , Haibo Li , Xian-Xi Zhang . Research on Kinetic and Thermodynamic Transformations of Organic-Inorganic Hybrid Materials for Fluorescent Anti-Counterfeiting Application information: Introducing a Comprehensive Chemistry Experiment. University Chemistry, 2024, 39(6): 390-399. doi: 10.3866/PKU.DXHX202403028
12. [12]
  You Wu , Chang Cheng , Kezhen Qi , Bei Cheng , Jianjun Zhang , Jiaguo Yu , Liuyang Zhang . ZnO/D-A共轭聚合物S型异质结高效光催化产H₂O₂及其电荷转移动力学研究. Acta Physico-Chimica Sinica, 2024, 40(11): 2406027-. doi: 10.3866/PKU.WHXB202406027
13. [13]
  Yan Li , Xinze Wang , Xue Yao , Shouyun Yu . Kinetic Resolution Enabled by Photoexcited Chiral Copper Complex-Mediated Alkene E→Z Isomerization: A Comprehensive Chemistry Experiment for Undergraduate Students. University Chemistry, 2024, 39(5): 1-10. doi: 10.3866/PKU.DXHX202309053
14. [14]
  Peng GENG , Guangcan XIANG , Wen ZHANG , Haichuang LAN , Shuzhang XIAO . Hollow copper sulfide loaded protoporphyrin for photothermal-sonodynamic therapy of cancer cells. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1903-1910. doi: 10.11862/CJIC.20240155
15. [15]
  Jin Tong , Shuyan Yu . Crystal Engineering for Supramolecular Chirality. University Chemistry, 2024, 39(3): 86-93. doi: 10.3866/PKU.DXHX202308113
16. [16]
  Yong Shu , Xing Chen , Sai Duan , Rongzhen Liao . How to Determine the Equilibrium Bond Distance of Homonuclear Diatomic Molecules: A Case Study of H₂. University Chemistry, 2024, 39(7): 386-393. doi: 10.3866/PKU.DXHX202310102
17. [17]
  Laiying Zhang , Yinghuan Wu , Yazi Yu , Yecheng Xu , Haojie Zhang , Weitai Wu . Innovation and Practice of Polymer Chemistry Experiment Teaching for Non-Polymer Major Students of Chemistry: Taking the Synthesis, Solution Property, Optical Performance and Application of Thermo-Sensitive Polymers as an Example. University Chemistry, 2024, 39(4): 213-220. doi: 10.3866/PKU.DXHX202310126
18. [18]
  Yang YANG , Pengcheng LI , Zhan SHU , Nengrong TU , Zonghua WANG . Plasmon-enhanced upconversion luminescence and application of molecular detection. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 877-884. doi: 10.11862/CJIC.20230440
19. [19]
  Yuhao SUN , Qingzhe DONG , Lei ZHAO , Xiaodan JIANG , Hailing GUO , Xianglong MENG , Yongmei GUO . Synthesis and antibacterial properties of silver-loaded sod-based zeolite. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 761-770. doi: 10.11862/CJIC.20230169
20. [20]
  Wenyan Dan , Weijie Li , Xiaogang Wang . The Technical Analysis of Visual Software ShelXle for Refinement of Small Molecular Crystal Structure. University Chemistry, 2024, 39(3): 63-69. doi: 10.3866/PKU.DXHX202302060

Get Citation

PDF

XML

Metrics

PDF Downloads(532)
Abstract views(728)
HTML views(38)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142