Citation: LUO Fang, GAO Jian, CHENG Yuan-Hua, CUI Wei, JI Ming-Juan. Interaction Mechanisms of Inhibitors of Glucoamylase by Molecular Dynamics Simulations and Free Energy Calculations[J]. Acta Physico-Chimica Sinica doi: 10.3866/PKU.WHXB201207063 shu

Interaction Mechanisms of Inhibitors of Glucoamylase by Molecular Dynamics Simulations and Free Energy Calculations

  • Received Date: 7 May 2012
    Available Online: 6 July 2012

    Fund Project: 国家自然科学基金(21173264) (21173264) 科技部重大专项(2009ZX09501-011) (2009ZX09501-011)中国科学院知识创新工程基金(ZNWH-2011-011)资助项目 (ZNWH-2011-011)

  • Sulfonium ion glucosidase inhibitors such as kotalanol (SK) and de-O-sulfonated kotalanol (DSK) are potential drug candidates for the treatment of type II diabetes, with no serious toxicity or side effects. Experimental binding assays against glucosidase show that the activity of DSK is slightly higher than that of SK, while the activity of the nitrogen analogue of de-O-sulfonated kotalanol (DSN) is ~1500-fold higher than that of the nitrogen analog of kotalanol (SN). Here, the binding mechanisms of four representative inhibitors of glucoamylase, SK, DSK, and their two nitrogen analogues, were explored in an integrated modeling study combining molecular dynamics (MD) simulations, binding free energy calculations, and binding free energy decomposition analysis. Our simulations highlight the significant impact of the combination of nitrogen substitution and sulfate anion group. Nitrogen substitution in the five-membered ring leads to the overturning of the polyhydroxylated chain, originating from the shorter bond length of N―C compared with S ― C, while the sulfate anion group restrains the freedom of the polyhydroxylated chain. These cumulative effects are able to significantly change the binding conformation of the inhibitor and substantially impair interactions between the inhibitor and glucosidase. The structural insights obtained in this study are expected to be valuable for increased understanding of the binding mechanism of sulfonium ion glucosidase inhibitors and future design of more potent glucosidase inhibitors.

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    1. [1]

      (1) Nichols, B. L.; Avery, S.; Sen, P.; Swallow, D. M.; Hahn, D.;Sterchi, E. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 1432. doi: 10.1073/pnas.0237170100

    2. [2]

      (2) Auricchio, S.; Semenza, G.; Rubino, A. Biochim. Biophys. Acta1965, 96, 498.

    3. [3]

      (3) Semenza, G.; Auricchio, S.; Rubino, A. Biochim. Biophys. Acta1965, 96, 487.

    4. [4]

      (4) Holman, R. R.; Cull, C. A.; Turner, R. C. Diabetes Care 1999,22, 960. doi: 10.2337/diacare.22.6.960

    5. [5]

      (5) Silva, C. H.; Taft, C. A. J. Biomol. Struct. Dyn. 2004, 22, 59.doi: 10.1080/07391102.2004.10506981

    6. [6]

      (6) Withers, S. G.; Namchuk, M.; Mosi, R. Potent GlycosideInhibitors: Transition State Mimics or Simply FortuitousBinders? In Iminosugars as Glycosidase Inhibitors; Arnold, E.S. Ed.;Wiley: New York, 2004; p 188.

    7. [7]

      (7) Matsuda, H.; Murakami, T.; Yashiro, K.; Yamahara, J.;Yoshikawa, M. Chem. Pharm. Bull. 1999, 47, 1725. doi: 10.1248/cpb.47.1725

    8. [8]

      (8) Wang, P. Y.; Kaneko, T.;Wang, Y.; Sato, A. Hepatology 1999,29, 161. doi: 10.1002/hep.510290109

    9. [9]

      (9) Yoshikawa, M.; Xu, F. M.; Nakamura, S.;Wang, T.; Matsuda,H.; Tanabe, G.; Muraoka, O. Heterocycles 2008, 75, 1397. doi: 10.3987/COM-07-11315

    10. [10]

      (10) Yoshikawa, M.; Murakami, T.; Shimada, H.; Matsuda, H.;Yamahara, J.; Tanabe, G.; Muraoka, O. Tetrahedron Lett. 1997,38, 8367. doi: 10.1016/S0040-4039(97)10270-2

    11. [11]

      (11) Matsuda, H.; Li, Y.; Murakami, T.; Matsumura, N.; Yamahara,J.; Yoshikawa, M. Chem. Pharm. Bull. 1998, 46, 1399. doi: 10.1248/cpb.46.1399

    12. [12]

      (12) Muraoka, O.; Xie,W. J.; Tanabe, G.; Amer, M. F. A.;Minematsu, T.; Yoshikawa, M. Tetrahedron Lett. 2008, 49,7315. doi: 10.1016/j.tetlet.2008.10.036

    13. [13]

      (13) Minami, Y.; Kurlyarna, C.; Ikeda, K.; Kato, A.; Takebayashi, K.;Adachi, I.; Fleet, G.W. J.; Kettawan, A.; Karnoto, T.; Asano, N.Bioorg. Med. Chem. 2008, 16, 2734. doi: 10.1016/j.bmc.2008.01.032

    14. [14]

      (14) Mohan, S.; Pinto, B. M. Carbohydr. Res. 2007, 342, 1551. doi: 10.1016/j.carres.2007.05.014

    15. [15]

      (15) Sim, L.; Jayakanthan, K.; Mohan, S.; Nasi, R.; Johnston, B. D.;Pinto, B. M.; Rose, D. R. Biochemistry-Us 2010, 49, 443. doi: 10.1021/bi9016457

    16. [16]

      (16) Mohan, S.; Jayakanthan, K.; Nasi, R.; Kuntz, D. A.; Rose, D.R.; Pinto, B. M. Org. Lett. 2010, 12, 1088. doi: 10.1021/ol100080m

    17. [17]

      (17) Yuasa, H.; Izumi, M.; Hashimoto, H. Curr. Top. Med. Chem.2009, 9, 76. doi: 10.2174/156802609787354270

    18. [18]

      (18) Case, D.; Darden, T. A.; Cheatham, T. E.; Simmerling, C.;Wang, J.; Duke, R.; Luo, R.; Crowley, M.;Walker, R.; Zhang,W.; Merz, K. M.;Wang, B.; Hayik, S.; Roitberg, A.; Seabra, G.;Kolossváry, I.;Wong, K. F.; Paesani, F.; Vanicek, J.;Wu, X.;Brozell, S.; Steinbrecher, T.; hlke, H.; Yang, L.; Tan, C.;Mongan, J.; Hornak, V.; Cui, G.; Mathews, D. H.; Seetin, M.G.; Sagui, C.; Babin, V.; Kollman, P. Amber 11; University ofCalifornia: San Francisco, 2010.

    19. [19]

      (19) Frisch, M. J.; Trucks, G.W.; Schlegel, H. B.; et al. Gaussian 03,Revision B.03; Gaussian Inc.:Wallingford, CT, 2004.

    20. [20]

      (20) Bayly, C. I.; Cieplak, P.; Cornell,W. D.; Kollman, P. A. J. Phys. Chem. 1993, 97, 10269. doi: 10.1021/j100142a004

    21. [21]

      (21) Wang, J. M.;Wolf, R. M.; Caldwell, J.W.; Kollman, P. A.; Case,D. A. J. Comput. Chem. 2004, 25, 1157. doi: 10.1002/jcc.20035

    22. [22]

      (22) Duan, Y.;Wu, C.; Chowdhury, S.; Lee, M. C.; Xiong, G. M.;Zhang,W.; Yang, R.; Cieplak, P.; Luo, R.; Lee, T.; Caldwell, J.;Wang, J. M.; Kollman, P. J. Comput. Chem. 2003, 24, 1999. doi: 10.1002/jcc.10349

    23. [23]

      (23) Jorgensen,W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R.W.; Klein, M. L. J. Chem. Phys. 1983, 79, 926. doi: 10.1063/1.445869

    24. [24]

      (24) Darden, T.; York, D.; Pedersen, L. J. Chem. Phys. 1993, 98,10089. doi: 10.1063/1.464397

    25. [25]

      (25) Eslami, H.; Mojahedi, F.; Moghadasi, J. J. Chem. Phys. 2010,133, 084105. doi: 10.1063/1.3474951

    26. [26]

      (26) Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. J. Comput. Phys. 1977, 23, 327. doi: 10.1016/0021-9991(77)90098-5

    27. [27]

      (27) Wang, J.; Hou, T.; Xu, X. Curr. Comput. Aided. Drug. Des.2006, 2, 287. doi: 10.2174/157340906778226454

    28. [28]

      (28) Kuhn, B.; Kollman, P. A. J. Med. Chem. 2000, 43, 3786. doi: 10.1021/jm000241h

    29. [29]

      (29) Huo, S.;Wang, J.; Cieplak, P.; Kollman, P. A.; Kuntz, I. D.J. Med. Chem. 2002, 45, 1412. doi: 10.1021/jm010338j

    30. [30]

      (30) Hou, T.; Yu, R. J. Med. Chem. 2007, 50, 1177. doi: 10.1021/jm0609162

    31. [31]

      (31) Kuhn, B.; Gerber, P.; Schulz-Gasch, T.; Stahl, M. J. Med. Chem.2005, 48, 4040. doi: 10.1021/jm049081q

    32. [32]

      (32) Hou, T.;Wang, J.; Li, Y.;Wang,W. J. Comput. Chem. 2011, 32,866. doi: 10.1002/jcc.21666

    33. [33]

      (33) Hou, T. J.; Xu, Z.; Zhang,W.; McLaughlin,W. A.; Case, D. A.;Xu, Y.;Wang,W. Mol. Cell. Proteomics 2009, 8, 639. doi: 10.1074/mcp.M800450-MCP200

    34. [34]

      (34) Hou, T. J.; Zhang,W.; Case, D. A.;Wang,W. J. Mol. Biol. 2008,376, 1201. doi: 10.1016/j.jmb.2007.12.054

    35. [35]

      (35) Hou, T. J.; Zhang,W.; Xu, X. J. J. Phys. Chem. B 2001, 105,5304. doi: 10.1021/jp0044476

    36. [36]

      (36) Hou, T. J.; Zhu, L. L.; Chen, L. R.; Xu, X. J. J. Chem. Inf. Comp. Sci. 2003, 43, 273. doi: 10.1021/ci025552a

    37. [37]

      (37) Wang, J. M.; Morin, P.;Wang,W.; Kollman, P. A. J. Am. Chem. Soc. 2001, 123, 5221. doi: 10.1021/ja003834q

    38. [38]

      (38) Hou, T.;Wang, J.; Li, Y.;Wang,W. J. Chem. Inf. Model. 2011,51, 69. doi: 10.1021/ci100275a

    39. [39]

      (39) Still,W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T.J. Am. Chem. Soc. 1990, 112, 6127. doi: 10.1021/ja00172a038

    40. [40]

      (40) Zhang,W.; Hou, T. J.; Qiao, X. B.; Xu, X. J. Acta Phys. -Chim. Sin. 2003, 19, 289. [章威, 侯廷军, 乔学斌, 徐筱杰. 物理化学学报, 2003, 19, 289.] doi: 10.3866/PKU.WHXB20030401

    41. [41]

      (41) Weiser, J.; Shenkin, P. S.; Still,W. C. J. Comput. Chem. 1999,20, 217. doi: 10.1002/(SICI)1096-987X(19990130)20:2<217::AID-JCC4>3.0.CO;2-A

    42. [42]

      (42) Onufriev, A.; Bashford, D.; Case, D. A. Proteins 2004, 55, 383.doi: 10.1002/prot.20033

    43. [43]

      (43) hlke, H.; Kiel, C.; Case, D. A. J. Mol. Biol. 2003, 330, 891.doi: 10.1016/S0022-2836(03)00610-7

    44. [44]

      (44) Sim, L.; Quezada-Calvillo, R.; Sterchi, E. E.; Nichols, B. L.;Rose, D. R. J. Mol. Biol. 2008, 375, 782. doi: 10.1016/j.jmb.2007.10.069

    45. [45]

      (45) Hou, T.; Qiao, X.; Zhang,W.; Xu, X. J. Phys. Chem. B 2002,106, 11295. doi: 10.1021/jp025595u

    46. [46]

      (46) Brady, G. P.; Sharp, K. A. J. Mol. Biol. 1995, 254, 77. doi: 10.1006/jmbi.1995.0600

    47. [47]

      (47) Yuasa, H.; Saotome, C.; Kanie, O. Trends Glycosci. Glycotechnol. 2002, 14, 231.

    48. [48]

      (48) Eskandari, R.; Jones, K.; Rose, D. R.; Pinto, B. M. Chem. Commun. 2011, 47, 9134. doi: 10.1039/c1cc13052h

    49. [49]

      (49) Rejto, P. A.; Verkhivker, G. M. Proteins 1997, 28, 313. doi: 10.1002/(SICI)1097-0134(199707)28:3<313::AID-PROT2>3.0.CO;2-D

    50. [50]

      (50) Pujadas, G.; Palau, J. Protein Sci. 2001, 10, 1645. doi: 10.1110/ps.8201


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