甲基多巴透过POPC磷脂双层膜过程的分子动力学模拟

doi:10.3866/PKU.WHXB201408271

Abstract

Abstract:

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.

Key words: Methyldopa, Hypertension, Cell membrane, POPC, Molecular simulation, Molecular dynamics

MSC2000:

O641

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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.

References

(1) Swift, P. A.; Macgregor, G. A. Journal of Renin-Angiotensin-Aldosterone System 2002, 3, 103. doi: 10.3317/jraas.2002.010
(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) Vedin, J. A.;Wilhelmsson, C. E.Werko, L. Brit. Heart J. 1973, 35, 1285. doi: 10.1136/hrt.35.12.1285
(4) Dollery, C. T.; Harington, M.; Hodge, J. V. Brit. Heart J. 1963, 25, 670. doi: 10.1136/hrt.25.5.670
(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
(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
(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
(10) Langer, S. Z.; Cavero, I.; Massingham, R. Hypertension 1980, 2, 372. doi: 10.1161/01.HYP.2.4.372
(11) Pollare, T.; Sithell, H.; Selnius, J.; Berne, C. Diabetologia 1988, 31, 415. doi: 10.1007/BF00271585
(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
(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
(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
(15) Lagunin, A. A.; Gomazkov, 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
(16) Ferrari, R.; Ceconi, C.; Curello, S.; Pepi, P.; Mazzoletti, A.; Visioli, O. Cardiovasc. Drugs. Ther. 1996, 10, 639. doi: 10.1007/BF00052511
(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
(19) Iliodromiti, S.; Mackenzie, F.; Lindsay, R. S. Drug Notes 2010, 27 (4), 166. (20) Mancia, G.; Ferrai, A.; Gregorin, 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
(23) Freed, C. R.;Wang, C. H.; U2Prichcrd, D. C.Hypertension 1984, 6, II34. (24) Robertson, D.; Tung, C. S.; Goldberg, 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
(27) Marrink, S. J.; Jaehnig, F.; Berendsen, H. J. C. Biophys. J. 1996, 71, 632. doi: 10.1016/S0006-3495(96)79264-0
(28) Zahn, D.; Brickmann, J. Chem. Phys. Lett. 2002, 352, 441. doi: 10.1016/S0009-2614(01)01437-3
(29) Bemporad, D.; Essex, J.W.; Luttmann, C. J. Phys. Chem. B 2004, 108, 4875. doi: 10.1021/jp035260s
(30) Shinoda,W.; Mikami, M.; Baba, T.; Hato, M. J. Phys. Chem. B 2004, 108, 9346. doi: 10.1021/jp035998+
(31) Nichols, J.W.; Deamer, D.W. Proc. Nat. Acad. Sci. U. S. A. 1980, 77, 2038. doi: 10.1073/pnas.77.4.2038
(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
(33) Jansen, M.; Blume, A. Biophys. J. 1995, 68, 997. doi: 10.1016/S0006-3495(95)80275-4
(34) Andrasko, J.; Forsén, S. Biochem. Biophys. Res. Commun. 1974, 60, 813. doi: 10.1016/0006-291X(74)90313-1
(35) Graziani, Y.; Livne, A. J. Membr. Biol. 1972, 7, 275. doi: 10.1007/BF01867920
(36) Khavrutskii, I. V.; Gorfe, A. A.; Lu, B.; McCammon, J. A. J. Am. Chem. Soc. 2009, 131, 1706. doi: 10.1021/ja8081704
(37) Papahadjopoulos, D.; Nir, S.; Ohki, S. Biochim. Biophys. Acta 1972, 266, 561. doi: 10.1016/0005-2736(72)90354-9
(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
(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
(41) Janosi, L.; Gorfe, A. A. J. Chem. Theory Comput. 2010, 6, 3267. doi: 10.1021/ct100381g
(42) Su, Z. Y.;Wang, Y. T. J. Phys. Chem. B 2011, 115, 796. doi: 10.1021/jp107599v
(43) Dunkin, C. M.; Pokorny, A.; Almeida, P. F.; Lee, H. S. J. Phys. Chem. B 2011, 115, 1188. doi: 10.1021/jp107763b
(44) Chen, R.; Poger, D.; Mark, A. E. J. Phys. Chem. B 2011, 115, 1038. doi: 10.1021/jp110002q
(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
(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
(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
(49) Manna, M.; Mukhopadhyay, C. Langmuir 2009, 25, 12235. doi: 10.1021/la902660q
(50) Hartshorn, M.; Jewett, C. M.; Brozik, J. A. Langmuir 2010, 26, 2609. doi: 10.1021/la904308g
(51) Mondal, S.; Mukhopadhyay, C. Langmuir 2008, 24, 10298. doi: 10.1021/la8015589
(52) Soemo, A. R.;Wirth, M. J. Langmuir 2010, 26, 2196. doi: 10.1021/la9038914
(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
(55) Carr, R.;Weinstock, I. A.; Sivaprasadarao, A.; Müller, A.; Aksimentiev, A. Nano Lett. 2008, 8, 3916. doi: 10.1021/nl802366k
(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
(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
(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
(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
(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
(65) Humphrey,W.; Dalke, A.; Schulten, K. J. Mol. Graph. 1996, 14, 33. doi: 10.1016/0263-7855(96)00018-5
(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
(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
(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
(70) Hub, J. S.; de Groot, B. L.; van der Spoel, D. J. Chem. Theory Comput. 2010, 6, 3713. doi: 10.1021/ct100494z
(71) Chiu, S.W.; Subramaniam, S.; Jakobsson, E. Biophys. J. 1999, 76, 1939. doi: 10.1016/S0006-3495(99)77353-4
(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
(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

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

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