Citation: DING Jun-Jie, DING Xiao-Qin, LI Da-Yu, PAN Li, CHEN Ji-Sheng. Quantitative Structure-Activity Relationship and Virtual Screening of ω-Conotoxins[J]. Acta Physico-Chimica Sinica, ;2014, 30(11): 2157-2167. doi: 10.3866/PKU.WHXB201409171 shu

Quantitative Structure-Activity Relationship and Virtual Screening of ω-Conotoxins

1.
State Key Laboratory of NBC Protection for Civilian, Beijing Institute of Pharmaceutical Chemistry, Beijing 102205, P. R. China

Received Date: 16 July 2014
Available Online: 17 September 2014

ω-Conotoxins are active peptides composed of 24-31 amino acids isolated from venomous marine predatory cone snails. ω-Conotoxins selectively inhibit voltage-gated calcium channels (VGCCs) in nociceptors, so are considered attractive molecules for drug design. In this study, based on a set of new amino acid structure descriptors (c-scales) and genetic partial least squares (G/PLS) regression method, quantitative structureactivity relationship (QSAR) models for N-type and P/Q-type VGCC anta nists of ω-conotoxins were developed. Two virtual polypeptide libraries with 2244 peptides were designed and established for N-type and P/Q-type VGCC anta nists, respectively. Then, based on the biological activities predicted from the constructed QSAR models and chemical similarities to the probes MVIIA and MVIIC, the polypeptide libraries were virtually screened. As a result, the established QSAR models had od predictability (cross- validated correlation coefficient CV-r²>0.89). The structural diversity of the libraries was validated using principal component analysis (PCA) and hierarchical cluster analysis (HCA) approaches. Six N-type and nineteen P/Q-type VGCC anta nists with high selectivity and activity were identified by virtual screening. The results of this study will be valuable for finding highly active polypeptide and non-peptide mimetics. Furthermore, the established polypeptide QSAR models and virtual screening strategy can also be applied to other peptide systems.
- ω-Conotoxin,
- Calcium channel anta nist,
- QSAR,
- Virtual screening
1. [1]
  
  (1) Vink, S.; Alewood, P. Br. J. Pharmacol. 2012, 167, 970. doi: 10.1111/j.1476-5381.2012.02082.x
2. [2]
  (2) Schroeder, C. I.; Lewis, R. J. Mar. Drugs 2006, 4, 193. doi: 10.3390/md403193
3. [3]
  (3) Tetsuyuki,W.; Junichi, A.; Takeshi, M.; Takashi, M.; Seiji, I. Neurochem. Res. 2003, 28, 705. doi: 10.1023/A:1022805615926
4. [4]
  (4) Lewis, R. J.; Dutertre, S.; Vetter, I.; Christie, M. J. Pharmacol. Rev. 2012, 64, 259.
5. [5]
  (5) Tetsuyuki,W.; Takashi, I.; Akinori, K.; Masayuki, X. M.; Yasuo, M.; Keiji, I.; Seiji, I. Neurochem. Res. 2005, 30, 1045. doi: 10.1007/s11064-005-7046-6
6. [6]
  (6) Obafemi, A.; Roth, B. Pain Med. 2013, 14, 447. doi: 10.1111/pme.2013.14.issue-3
7. [7]
  (7) Bourinet, E.; Zamponi, G.W. Curr. Top. Med. Chem. 2005, 5, 539. doi: 10.2174/1568026054367610
8. [8]
  (8) Lynch, S. S.; Cheng, C. M.; Yee, J. L. Ann. Pharmacother. 2006, 40, 1293. doi: 10.1345/aph.1G584
9. [9]
  (9) Alicino, I.; Giglio, M.; Manca, F.; Bruno, F.; Puntillo, F. Pain 2012, 153, 245. doi: 10.1016/j.pain.2011.10.002
10. [10]
  (10) Sanford, M. CNS Drugs 2013, 27, 989. doi: 10.1007/s40263-013-0107-5
11. [11]
  (11) Sasaki, T.; Kobayashi, K.; Kohno, T.; Sato, K. FEBS Lett. 2000, 466, 125. doi: 10.1016/S0014-5793(99)01772-X
12. [12]
  (12) Wang, C. Z.; Jiang, H.; Qi, Z.W. Prog. Biochem. Biophys. 2003, 30, 537. [王承忠, 蒋辉, 戚正武. 生物化学与生物物理进展, 2003, 30, 537.]
13. [13]
  (13) Kolosov, A.; Aurini, L.;Williams, E. D.; Cooke, I.; odchild, C. S. Pain Med. 2011, 12, 923. doi: 10.1111/pme.2011.12.issue-6
14. [14]
  (14) Fedosova, A. E.; Moshkovskiic, S. A.; Kuznetsovac, K. G.; Oliverab, B. M. Biochemistry-Moscow+Series B: Biomed. Chem. 2012, 6, 107.
15. [15]
  (15) Kolosov, A.; odchild, C. S.; Cooke, I. Pain Med. 2010, 11, 262. doi: 10.1111/pme.2010.11.issue-2
16. [16]
  (16) Zhan, D. L;Wang, S.; Han,W.W.; Liu, J. S. Acta Chim. Sin. 2012, 70, 217. [詹冬玲, 王嵩, 韩葳葳, 刘景圣, 化学学报, 2012, 70, 217.] doi: 10.6023/A1108313
17. [17]
  (17) Zhang, Q. Q.; Yao, Q. Z.; Zhang, S. P.; Bi, L. M.; Zhou, Z. G.; Zhang, J. Acta Phys. -Chim. Sin. 2014, 30, 371. [张青青, 姚其正, 张生平, 毕乐明, 周之光, 张骥. 物理化学学报, 2014, 30, 371.] doi: 10.3866/PKU.WHXB201312192
18. [18]
  (18) Hou, T. J.; Xu, X. J. Curr. Pharm. Des. 2004, 10, 1011. doi: 10.2174/1381612043452721
19. [19]
  (19) Ding, J. J.; Ding, X. Q.; Zhao, L. F.; Chen, J. S. Prog. Chem. 2005, 17, 130. [丁俊杰, 丁晓琴, 赵立峰, 陈冀胜. 化学进展, 2005, 17, 130.]
20. [20]
  (20) Audie, J.; Swanson, J. Chem. Biol. Drug. Des. 2013, 81, 50. doi: 10.1111/cbdd.2012.81.issue-1
21. [21]
  (21) Hou, T. J.; Li, N.; Li, Y. Y.;Wang,W. J. Proteome Res. 2012, 11, 2982. doi: 10.1021/pr3000688
22. [22]
  (22) Hou, T. J.; Li, Y. Y.;Wang,W. Bioinformatics 2011, 27, 1814. doi: 10.1093/bioinformatics/btr294
23. [23]
  (23) 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
24. [24]
  (24) Ding, J. J.; Ding, X. Q.; Zhao, L. F.; Chen, J. S. Acta Pharm. Sin. 2005, 40, 340. [丁俊杰, 丁晓琴, 赵立峰, 陈冀胜. 药学学报, 2005, 40, 340.]
25. [25]
  (25) Atkinson, R. A.; Kieffer, B.; Dejaegere, A.; Sirockin, F.; Lefevre, J. F. Biochemistry 2000, 39, 3908. doi: 10.1021/bi992651h
26. [26]
  (26) Nielsen, K. J.; Adams, D.; Thomas, L.; Bond, T.; Alewood, P. F.; Craik, D. J.; Lewis, R. J. J. Mol. Biol. 1999, 289, 1405. doi: 10.1006/jmbi.1999.2817
27. [27]
  (27) Richard, J. L.; Katherine, J. N.; David, J. C.; Marion, L. L.; Denise, A. A.; Iain, A. S.; Tudor, L.; David, J. A.; Trudy, B.; Linda, T.; Aluu, J.; Jodi-Lea, M.; Roger, D.; Peter, R. A.; Paul, F. A. J. Biol. Chem. 2000, 275, 35335. doi: 10.1074/jbc.M002252200
28. [28]
  (28) Mason, J. S. Computer-Assisted Drug Design; Science Press: Beijing, 2007; p 307.
29. [29]
  (29) Cerius 2 User Guide; Molecular Simulations Inc: San Die , 2000.
30. [30]
  (30) Drwal, M. N.; Griffith, R. Drug Discovery Today: Technologies 2013, 10, e395.
31. [31]
  (31) Wilson, G. L.; Lill, M. A. Future Med. Chem. 2011, 3, 735. doi: 10.4155/fmc.11.18
32. [32]
  (32) G rge, P. M.; Ramachandran, J. Annu. Rev. Pharmacol. Toxicol. 1995, 35, 307. doi: 10.1146/annurev.pa.35.040195.001515
33. [33]
  (33) Pallaghy, P. K.; Nielsen, K. J.; Craik, D. J.; Norton, R. S. Protein Sci. 1994, 3, 1833. doi: 10.1002/pro.v3:10
34. [34]
  (34) Adams, D. J.; Berecki, G. Biochim. Biophys. Acta 2013, 1828, 1619. doi: 10.1016/j.bbamem.2013.01.019
35. [35]
  (35) Kazuki, S.; Cecile, R.; Nicole, M. M.; Toru, S.; Akira, O.; Atsuko, O.; Jae, I. K.; Toshiyuki, K.; Masami, T.; Michael, S. FEBS Lett. 1997, 414, 480. doi: 10.1016/S0014-5793(97)01056-9
36. [36]
  (36) Nielsen, K. J.; Adams, D. A.; Alewood, P. F.; Lewis, R. J.; Thomas, L.; Schroeder, T.; Craik, D. J. Biochemistry 1999, 38, 6741. doi: 10.1021/bi982980u
37. [37]
  (37) Mould, J.; Yasuda, T.; Schroeder, C. I.; Beedle, A. M.; Doering, C. J.; Zamponi, G.W.; Adams, D. J.; Lewis, R. J. J. Biol. Chem. 2004, 279, 34705.
38. [38]
  (38) Van Petegem, F.; Minor, D. L. Biochem. Soc. Trans. 2006, 34, 887. doi: 10.1042/BST0340887
39. [39]
  (39) Kajuti, S.; Cecile, R.; Nicole, M. M.; Toru. S.; Atsuko, O. FEBS Lett. 2000, 469, 147. doi: 10.1016/S0014-5793(00)01263-1
40. [40]
  (40) Kazuki, S.; Cecile, R.; Nicole, M. M.; Toru, S.; Atsuko, O.; Kazushi, M.; Catherine, V. R.; Masami, T.; Michael, J. S. Biochem. Biophys. Res. Commun. 2000, 269, 254. doi: 10.1006/bbrc.2000.2284
41. [41]
  (41) Lew, M. J.; Flinn, J. P.; Pallaghy, P. K.; Murphy, R.; Whorlow, S. L.;Wright, C. E.; Norton, R. S.; Angus, J. A. J. Biol. Chem. 1997, 272, 12014. doi: 10.1074/jbc.272.18.12014
42. [42]
  (42) Nadasdi, L.; Yamashiro, D.; Chung, D.; Tarczy-Hornoch, K.; Adriaenssens, P.; Ramachandran, J. Biochemistry 1995, 34, 8076. doi: 10.1021/bi00025a013
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