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]
  Tiejin Chen , Xiaokuang Xue , Jian Li , Minhui Cui , Yongliang Hao , Mianqi Xue , Haihua Xiao , Jiechao Ge , Pengfei Wang . Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy. Acta Physico-Chimica Sinica, 2025, 41(10): 100113-0. doi: 10.1016/j.actphy.2025.100113
4. [4]
  Xiaochen Zhang , Fei Yu , Jie Ma . Cutting-Edge Applications of Multi-Angle Numerical Simulations for Capacitive Deionization. Acta Physico-Chimica Sinica, 2024, 40(11): 2311026-0. doi: 10.3866/PKU.WHXB202311026
5. [5]
  Yaping Li , Sai An , Aiqing Cao , Shilong Li , Ming Lei . The Application of Molecular Simulation Software in Structural Chemistry Education: First-Principles Calculation of NiFe Layered Double Hydroxide. University Chemistry, 2025, 40(3): 160-170. doi: 10.12461/PKU.DXHX202405185
6. [6]
  Shanghua Li , Malin Li , Xiwen Chi , Xin Yin , Zhaodi Luo , Jihong Yu . High-Stable Aqueous Zinc Metal Anodes Enabled by an Oriented ZnQ Zeolite Protective Layer with Facile Ion Migration Kinetics. Acta Physico-Chimica Sinica, 2025, 41(1): 100003-0. doi: 10.3866/PKU.WHXB202309003
7. [7]
  Xiaodong Chen , Yumin Zhang . An Improved Simulated Annealing Algorithm for Predicting the Molecular Formulas of Organic Compounds. University Chemistry, 2025, 40(9): 19-24. doi: 10.12461/PKU.DXHX202408095
8. [8]
  Yaling Chen . Basic Theory and Competitive Exam Analysis of Dynamic Isotope Effect. University Chemistry, 2024, 39(8): 403-410. doi: 10.3866/PKU.DXHX202311093
9. [9]
  Jiayu Gu , Siqi Wang , Jun Ling . Kinetics of Living Copolymerization: A Brief Discussion. University Chemistry, 2025, 40(4): 100-107. doi: 10.12461/PKU.DXHX202406012
10. [10]
  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
11. [11]
  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
12. [12]
  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
13. [13]
  Jiageng Li , Putrama . 数值积分耦合非线性最小二乘法一步确定反应动力学参数. University Chemistry, 2025, 40(6): 364-370. doi: 10.12461/PKU.DXHX202407098
14. [14]
  Wenwen Zhang , Peichao Zhang , Conghao Gai , Xiaoyun Chai , Yan Zou , Qingjie Zhao . Unveiling Kinetics at Natural Abundance: ¹³C NMR Isotope Effect Experiments. University Chemistry, 2025, 40(10): 203-207. doi: 10.12461/PKU.DXHX202411076
15. [15]
  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
16. [16]
  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
17. [17]
  Jiajie Cai , Chang Cheng , Bowen Liu , Jianjun Zhang , Chuanjia Jiang , Bei Cheng . CdS/DBTSO-BDTO S-scheme photocatalyst for H₂ production and its charge transfer dynamics. Acta Physico-Chimica Sinica, 2025, 41(8): 100084-0. doi: 10.1016/j.actphy.2025.100084
18. [18]
  Jichao XU , Ming HU , Xichang CHEN , Chunhui WANG , Leichen WANG , Lingyi ZHOU , Xing HE , Xiamin CHENG , Su JING . Construction and hydrogen peroxide-activated chemodynamic activity of ferrocene?benzoselenadiazole conjugate. Chinese Journal of Inorganic Chemistry, 2025, 41(8): 1495-1504. doi: 10.11862/CJIC.20250144
19. [19]
  Linlin Wu , Yonghua Zhou , Zhongbei Li , Liu Deng , Younian Liu , Limiao Chen , Jianhan Huang . Digital Education Promoting Applied Chemistry Comprehensive Experiments: A Case Study of Catalytic Oxidation of Hydrogen Chloride and Reaction Kinetics. University Chemistry, 2025, 40(9): 273-278. doi: 10.12461/PKU.DXHX202411018
20. [20]
  Xinyu Xu , Jiale Lu , Bo Su , Jiayi Chen , Xiong Chen , Sibo Wang . Steering charge dynamics and surface reactivity for photocatalytic selective methane oxidation to ethane over Au/Ti-CeO₂. Acta Physico-Chimica Sinica, 2025, 41(11): 100153-0. doi: 10.1016/j.actphy.2025.100153

Get Citation

PDF

XML

Metrics

PDF Downloads(532)
Abstract views(916)
HTML views(67)

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