Citation: ZHAO Teng-Teng, YANG Xue-Yu, DONG Ke-Ke, ZHU Xiao-Lei. Interaction Mechanism Between AChE and 1, 7-Diazacarbazole Inhibitors Based on Molecular Dynamics Simulations[J]. Chinese Journal of Inorganic Chemistry, ;2017, 33(11): 2065-2074. doi: 10.11862/CJIC.2017.250 shu

Interaction Mechanism Between AChE and 1, 7-Diazacarbazole Inhibitors Based on Molecular Dynamics Simulations

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China

Corresponding author: ZHU Xiao-Lei, xlzhu@njtech.edu.cn
Received Date: 31 August 2017
Revised Date: 27 September 2017

Figures(7)

The molecular docking, molecular dynamics (MD) simulation, and binding free energy analysis are used to gain the insight into the binding mechanism of three 1, 7-diazacarbazole derivatives (marked as M1, M2, and M3, respectively) with AChE at the atom level. The electrostatic and van der Waals (vdW) interactions of the three inhibitors with AChE are analyzed and discussed. The ranking of the computed binding free energies based on MM-PBSA method is consistent with the ranking of experimental bioactivities for the three inhibitors. The hydrogen-bond interactions of the inhibitors with S286 are favorable to the binding affinity of inhibitors to AChE. The van der Waals interactions, especially the key contacts with W279 and Y334 have larger contributions to the binding free energy and play an important role in distinguishing the bioactivities of M1(or M2) and M3.
- Alzheimer's disease,
- AChE,
- 1, 7-diazacarbazole inhibitor,
- molecular dynamics simulation,
- MM-PBSA
1. [1]
  Mussele S V D, Bastard N L, Vermeiren Y, et al. Int. J. Geriatr. Psychiatr., 2013, 28(3):265-275 doi: 10.1002/gps.v28.3
2. [2]
  Sperling R A, Dickerson B C, Pihlajamaki M, et al. Neuromol. Med., 2010, 12(1):27-43 doi: 10.1007/s12017-009-8109-7
3. [3]
  Nestor P J, Fryer T D, Hodges J R. NeuroImage., 2006, 30 (3):1010-1020 doi: 10.1016/j.neuroimage.2005.10.008
4. [4]
  Bartus R T, Dean R L, Beer B, et al. Science, 1982, 217 (4558):408-414 doi: 10.1126/science.7046051
5. [5]
  Terry R D, Masliah E, Salmon D P, et al. Ann. Neurol., 1991, 30(4):572-580 doi: 10.1002/(ISSN)1531-8249
6. [6]
  Francis P T, Palmer A M, Snape M, et al. J. Neurol. Neurosur. Ps., 1999, 67(4):558-558 doi: 10.1136/jnnp.67.4.558
7. [7]
  Talesa V N. Mech. Ageing Dev., 2001, 122(16):1961-1969 doi: 10.1016/S0047-6374(01)00309-8
8. [8]
  Alipour M, Khoobi M, Moradi A, et al. Eur. J. Med. Chem., 2014, 82:536-544 doi: 10.1016/j.ejmech.2014.05.056
9. [9]
  Liu S, Shang R, Shi L, et al. Eur. J. Med. Chem., 2014, 81: 237-244 doi: 10.1016/j.ejmech.2014.05.020
10. [10]
  Akrami H, Mirjalili B F, Khoobi M, et al. Eur. J. Med. Chem., 2014, 84:375-381 doi: 10.1016/j.ejmech.2014.01.017
11. [11]
  Wang C, Wu Z, Cai H, et al. Bioorg. Med. Chem. Lett., 2015, 25(22):5212-5216 doi: 10.1016/j.bmcl.2015.09.063
12. [12]
  Hong C, Luo W, Yao D, et al. Bioorg. Med. Chem., 2014, 22 (12):3213-3219 doi: 10.1016/j.bmc.2014.03.045
13. [13]
  Giacobini E. Neurochem. Res., 2003, 28(3):515-522
14. [14]
  Xie S S, Wang X B, Jiang N, et al. Eur. J. Med. Chem., 2015, 95:153-165 doi: 10.1016/j.ejmech.2015.03.040
15. [15]
  Alpan A S, Parlar S, Carlino L, et al. Bioorgan. Med. Chem., 2013, 21(17):4928-4937 doi: 10.1016/j.bmc.2013.06.065
16. [16]
  Mohammadi-Khanaposhtani M, Saeedi M, Zafarghandi N S, et al. Eur. J. Med. Chem., 2015, 92:799-806 doi: 10.1016/j.ejmech.2015.01.044
17. [17]
  Asadipour A, Alipour M, Jafari M, et al. Eur. J. Med. Chem., 2013, 70:623-630 doi: 10.1016/j.ejmech.2013.10.024
18. [18]
  Gao X, Zhou C, Liu H, et al. J. Enzyme Inhib. Med. Chem., 2017, 32(1):146-152 doi: 10.1080/14756366.2016.1243534
19. [19]
  Liu H, Liu L, Gao X, et al. Eur. J. Med. Chem., 2017, 126: 810-822 doi: 10.1016/j.ejmech.2016.12.003
20. [20]
  Gazzard L, Williams K, Chen H F, et al. J. Med. Chem., 2015, 58(12):5053-5074 doi: 10.1021/acs.jmedchem.5b00464
21. [21]
  Niu C, XU Y, Xu Y, et al. J. Phys. Chem. B, 2005, 109(49): 23730-23738 doi: 10.1021/jp0552877
22. [22]
  Puiatti M, Borioni J L, Vallejo M G, et al. J. Mol. Graph. Model., 2013, 44:136-144 doi: 10.1016/j.jmgm.2013.05.009
23. [23]
  Zhu X L, Yu N X, Hao G F, et al. J. Mol. Graph. Model., 2013, 41:55-60 doi: 10.1016/j.jmgm.2013.01.004
24. [24]
  Zhou A, Hu J, Wang L, et al. J. Mol. Model., 2015, 21(10): 277 doi: 10.1007/s00894-015-2797-8
25. [25]
  Shi J, Tu W, Luo M, et al. Mol. Simul., 2016, 43(2):102-109
26. [26]
  Mohammadi T, Ghayeb Y. J. Biomol. Struct. Dyn., 2017:1-13
27. [27]
  Hossain T, Saha A, Mukherjee A. J. Biomol. Struct. Dyn., 2017:1-12
28. [28]
  El-Malah A, Gedawy E M, Kassab A E, et al. Arch. Pharm. Chem. Life Sci., 2014, 347(2):96-103 doi: 10.1002/ardp.v347.2
29. [29]
  Molinuevo J L, Berthier M L, Rami L. Arch. Gerontol. Geriatr., 2011, 52(1):18-22 doi: 10.1016/j.archger.2009.11.004
30. [30]
  Knowles J. Core Evidence, 2006, 1(3):195-219
31. [31]
  Marco L, Carreiras M C. Recent Pat. CNS Drug. Discovery, 2006, 1(1):105-111 doi: 10.2174/157488906775245246
32. [32]
  Wolfson C, Oremus M, Shukla V, et al. Clin. Ther., 2002, 24 (6):862-886 doi: 10.1016/S0149-2918(02)80004-2
33. [33]
  Bono G F, Simo-Silva D P, Batistela M S, et al. Neurochem. Int., 2015, 81:57-62 doi: 10.1016/j.neuint.2014.12.009
34. [34]
  Kryger G, Silman I, Sussman J L. Structure, 1999, 7(3):297-307 doi: 10.1016/S0969-2126(99)80040-9
35. [35]
  Larkin M, Blackshields G, Brown N P, et al. Bioinformatics, 2007, 23:2947-2948 doi: 10.1093/bioinformatics/btm404
36. [36]
  Morris G M, Goodsell D S, Halliday R S, et al. J. Comput. Chem., 1998, 19(14):1639-1662 doi: 10.1002/(ISSN)1096-987X
37. [37]
  Cornell W D, Cieplak P, Bayly C I, et al. J. Am. Chem. Soc., 1995, 117(19):5179-5197 doi: 10.1021/ja00124a002
38. [38]
  Wang J, Wolf R M, Caldwell J W, et al. J. Comput. Chem., 2004, 25(9):1157-1174 doi: 10.1002/(ISSN)1096-987X
39. [39]
  Bayly C I, Cieplak P, Cornell W, et al. J. Phys. Chem., 1993, 97(40):10269-10280 doi: 10.1021/j100142a004
40. [40]
  Jorgensen W L, Chandrasekhar J, Madura J D, et al. J. Chem. Phys., 1983, 79(2):926-935 doi: 10.1063/1.445869
41. [41]
  Rycaert J P, Ciccotti G, Berendsen H J C. J. Comput. Phys., 1977, 23:327-341 doi: 10.1016/0021-9991(77)90098-5
42. [42]
  York D M, Darden T A, Pedersen L G. J. Chern. Phys., 1993, 99(10):8345-8348 doi: 10.1063/1.465608
43. [43]
  Kumari R, Kumar R, Open Source Drug Discovery Consortium, et al. J. Chem. Inf. Model., 2014, 54(7):1951-1962 doi: 10.1021/ci500020m
44. [44]
  Saíz-Urra L, Cabrera M A, Froeyen M. J. Mol. Graph. Model., 2011, 29(5):726-739 doi: 10.1016/j.jmgm.2010.12.005
45. [45]
  El-Barghouthi M I, Jaime C, Al-Sakhen N A, et al. J. Mol. Struct. THEOCHEM, 2008, 853(1):45-52
46. [46]
  Fajer P, Fajer M, Zawrotny M, et al. Methods Enzymol., 2015, 563:623-642 doi: 10.1016/bs.mie.2015.07.030
47. [47]
  Sa R, Fang L, Huang M, et al. J. Phys. Chem. A, 2014, 118: 9113-9119 doi: 10.1021/jp5064319
48. [48]
  Jamshidi S, Rafii-Tabar H, Jalili S. Mol. Simul., 2013, 40: 469-476
49. [49]
  Lobanov M Y, Bogatyreva N S, Galzitskaya O V. Mol. Biol., 2008, 42(4):623-628 doi: 10.1134/S0026893308040195
50. [50]
  Hu G D, Zhu T, Zhang S L, et al. Eur. J. Med. Chem., 2010, 45(1):227-235 doi: 10.1016/j.ejmech.2009.09.048
51. [51]
  Wu E L, Han K L, Zhang J Z H. Chem. Eur. J., 2008, 14 (28):8704-8714 doi: 10.1002/chem.v14:28
52. [52]
  Laskowski R A, Swindells M B. J. Chem. Inf. Model., 2011, 51:2778-2786 doi: 10.1021/ci200227u
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