Citation: CONG Yong, XUE Ying. Quantitative Structure-Activity Relationship Study of the Non-Nucleoside Inhibitors of HCV NS5B Polymerase by Machine Learning Methods[J]. Acta Physico-Chimica Sinica, ;2013, 29(08): 1639-1647. doi: 10.3866/PKU.WHXB201305171 shu

Quantitative Structure-Activity Relationship Study of the Non-Nucleoside Inhibitors of HCV NS5B Polymerase by Machine Learning Methods

CONG Yong ¹ ,
XUE Ying ^1,2,

1.
1 College of Chemistry, Key Laboratory of Green Chemistry and Technology, Ministry of Education, Sichuan University, Chengdu 610064, P. R. China;
2 State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, P. R. China

Received Date: 1 February 2013
Available Online: 17 May 2013
Fund Project: 国家自然科学基金(21173151) (21173151)西华大学先进科学计算省重点实验室开放基金(szjj2011-029)资助项目 (szjj2011-029)

The quantitative structure-activity relationship (QSAR) approach was used to predict the activity of two different scaffolds (benzoisothiazole and benzothiazine) of 89 non-nucleoside inhibitors of hepatitis c virus (HCV) NS5B polymerase. Two selection methods, linear stepwise regression analysis (LSRA) and genetic al rithm-partial least squares (GA-PLS), were used to select appropriate descriptor subsets for QSAR modeling with linear models. The genetic al rithm-support vector machine (GA-SVM) approach was first used to build nonlinear models with six LSRA- and seven GA-PLS-selected descriptors. Three QSAR models built with the six LSRA-selected descriptors gave correlation coefficients of 0.958-0.962 for the training set. GA-SVM provided the highest prediction accuracy of the models of 0.962. Three QSAR models built with the seven GA-PLS-selected descriptors gave correlation coefficients of 0.918-0.960 for the training set, of which the partial least squares (PLS) model was the best (0.960). The investigated models gave satisfactory prediction results and can be extended to other QSAR studies.
- HCV NS5B polymerase,
- Non-nucleoside Inhibitor,
- Linear stepwise regression analysis,
- Partial least square,
- Genetic al rithm,
- Support vector machine
1. [1]
  
  (1) Choo, Q. L.;Weiner, A. J.; Overby, L. R.; Bradley, D.W.;Houghton, M. Science 1989, 244, 359. doi: 10.1126/science.2523562
2. [2]
  (2) (a) Lauer, G. M.;Walker, B. D. N. Engl. J. Med. 2001, 345, 41.doi: 10.1056/NEJM200107053450107
3. [3]
  (b) Di Bisceglie, A. M. Lancet 1998, 351, 351.
4. [4]
  (c) Alter, M. J.; Kruszon-Moran, D.; Nainan, O. V.; McQuillan,G. M.; Gao, F.; Moyer, L. A.; Kaslow, R. A.; Mar lis, H. S.N. Engl. J. Med. 1999, 341, 556.
5. [5]
  (3) Manns, M. P.; McHutchison, J. G.; rdon, S. C.; Rustgi, V. K.;Shiffman, M.; Reindollar, R.; odman, Z. D.; Koury, K.; Ling,M. H.; Albrecht, J. K. Lancet 2002, 347, 975.
6. [6]
  (4) (a) Koch, U.; Narjes, F. Curr. Top. Med. Chem. 2007, 7, 1302.doi: 10.2174/156802607781212211
7. [7]
  (b) Rönn, R.; Sandström, A. Curr. Top. Med. Chem. 2008, 8, 533.
8. [8]
  (c) Zapf, C.W.; Bloom, J. D.; Levin, J. I. Ann. Rep. Med. Chem.2007, 42, 281.
9. [9]
  (5) Appel, N.; Schaller, T.; Penin, F.; Bartenschlager, R. J. Biol. Chem. 2006, 281, 9833. doi: 10.1074/jbc.R500026200
10. [10]
  (6) Ni, Z. J.;Wagman, A. S. Curr. Opin. Drug Discov. Dev. 2004, 7,446.
11. [11]
  (7) Beaulieu, P. L.; Bos, M.; Bousquet, Y.; Fazal, G.; Gauthier, J.;Gillard, J.; ulet, S.; LaPlante, S.; Poupart, M. A.; Lefebvre,S.; McKercher, G.; Pellerin, C.; Austel, V.; Kukolj, G. Bioorg. Med. Chem. Lett. 2004, 14, 119. doi: 10.1016/j.bmcl.2003.10.023
12. [12]
  (8) Stansfield, I.; Ercolani, C.; Mackay, A.; Conte, I.; Pompei, M.;Koch, U.; Gennari, N.; Giuliano, C.; Rowley, M.; Narjes, F.Bioorg. Med. Chem. Lett. 2009, 19, 627. doi: 10.1016/j.bmcl.2008.12.068
13. [13]
  (9) Louise-May, S.; Yang,W.; Nie, X.; Liu, D.; Deshpande, M. S.;Phadke, A. S.; Huang, M.; Agarwal, A. Bioorg. Med. Chem. Lett. 2007, 17, 3905. doi: 10.1016/j.bmcl.2007.04.103
14. [14]
  (10) Stankiewicz-Dro n, A.; Palchykovska, L. G.; Kostina, V. G.;Alexeeva, I. V.; Shved, A. D.; Boguszewska-Chachulska, A. M.Bioorg. Med. Chem. 2008, 16, 8846. doi: 10.1016/j.bmc.2008.08.074
15. [15]
  (11) Bosse, T. D.; Larson, D. P.;Wagner, R.; Hutchinson, D. K.;Rockway, T.W.; Kati,W. M.; Liu, Y.; Masse, S.; Middleton, T.;Mo, H.; Mont mery, D.; Jiang,W.; Koev, G.; Kempf, D. J.;Molla, A. Bioorg. Med. Chem. Lett. 2008, 18, 568. doi: 10.1016/j.bmcl.2007.11.088
16. [16]
  (12) Lü,W. J.; Chen, Y. L.; Ma,W. P.; Zhang, X. Y.; Luan, F.; Liu,M. C.; Chen, X. G.; Hu, Z. D. Euro. J. Med. Chem. 2008, 43,569. doi: 10.1016/j.ejmech.2007.04.011
17. [17]
  (13) Luan, F.; Liu, H. T.; Ma,W. P.; Fan, B. T. Euro. J. Med. Chem.2008, 43, 43. doi: 10.1016/j.ejmech.2007.03.002
18. [18]
  (14) Melagraki, G.; Afantitis, A.; Sarimveis, H.; Koutentis, P. A.;Markopoulos, J.; Igglessi-Markopoulou, O. Bioorg. Med. Chem.2007, 15, 7237. doi: 10.1016/j.bmc.2007.08.036
19. [19]
  (15) Su, L.; Li, L.; Li, Y.; Zhang, X.; Huang, X.; Zhai, H. Med. Chem. Res. 2012, 21, 2079. doi: 10.1007/s00044-011-9734-x
20. [20]
  (16) de Vicente, J.; Hendricks, R. T.; Smith, D. B.; Fell, J. B.; Fischer,J.; Spencer, S. R.; Stengel, P. J.; Mohr, P.; Robinson, J. E.;Blake, J. F.; Hilgenkamp, R. K.; Yee, C.; Adjabeng, G.;Elworthy, T. R.; Li, J.;Wang, B.; Bamberg, J. T.; Harris, S. F.;Wong, A.; Leveque, V. J. P.; Najera, I.; Pogam, S. L.;Rajyaguru, S.; Ao-Ieong, G.; Alexandrova, L.; Larrabee, S.;Brandl, M.; Briggs, A.; Sukhtankar, S.; Farrell, R. Bioorg. Med. Chem. Lett. 2009, 19, 5652. doi: 10.1016/j.bmcl.2009.08.022
21. [21]
  (17) Hendricks, R. T.; Spencer, S. R.; Blake, J. F.; Fell, J. B.; Fischer,J.; Stengel, P. J.; Leveque, V. J. P.; Pogam, S. L.; Rajyaguru, S.;Najera, I.; Swallow, S. Bioorg. Med. Chem. Lett. 2009, 19, 410.doi: 10.1016/j.bmcl.2008.11.060
22. [22]
  (18) de Vicente, J.; Hendricks, R. T.; Smith, D. B.; Fell, J. B.; Fischer,J.; Spencer, S. R.; Stengel, P. J.; Mohr, P.; Robinson, J. E.;Blake, J. F.; Hilgenkamp, R. K.; Yee, C.; Adjabeng, G.;Elworthy, T. R.; Tracy, J.; Chin, E.; Li, J.;Wang, B.; Bamberg,J. T.; Stephenson, R.; Oshiro, C.; Harris, S. F.; Ghate, M.;Leveque, V.; Najera, I.; Pogam, S. L.; Rajyaguru, S.; Ao-Ieong,G.; Alexandrova, L.; Larrabee, S.; Brandl, M.; Briggs, A.;Sukhtankar, S.; Farrell, R.; Xu, B. Bioorg. Med. Chem. Lett.2009, 19, 3642. doi: 10.1016/j.bmcl.2009.05.004
23. [23]
  (19) Hendricks, R. T.; Fell, J. B.; Blake, J. F.; Fischer, J. P.;Robinson, J. E.; Spencer, S. R.; Stengel, P. J.; Bernacki, A. L.;Leveque, V. J. P.; Pogam, S. L.; Rajyaguru, S.; Najera, I.; Josey,J. A.; Harris, J. R.; Swallow, S. Bioorg. Med. Chem. Lett. 2009,19, 3637. doi: 10.1016/j.bmcl.2009.04.119
24. [24]
  (20) de Vicente, J.; Hendricks, R. T.; Smith, D. B.; Fell, J. B.; Fischer,J.; Spencer, S. R.; Stengel, P. J.; Mohr, P.; Robinson, J. E.;Blake, J. F.; Hilgenkamp, R. K.; Yee, C.; Zhao, J.; Elworthy, T.R.; Tracy, J.; Chin, E.; Li, J.; Lui, A.;Wang, B.; Oshiro, C.;Harris, S. F.; Ghate, M.; Leveque, V. J. P.; Najera, I.; Pogam, S.L.; Rajyaguru, S.; Ao-Ieong, G.; Alexandrova, L.; Fitch, B.;Brandl, M.; Masjedizadeh, M.;Wua, S. Y.; de Keczer, S.;Voronin, T. Bioorg. Med. Chem. Lett. 2009, 19, 5648.doi: 10.1016/j.bmcl.2009.08.023
25. [25]
  (21) Todeschini, R.; Consonni, V. Handbook of Molecular Descriptors;Wiley-VCH: New York, 2000.
26. [26]
  (22) Xue, Y.; Li, Z. R.; Yap, C.W.; Sun, L. Z.; Chen, X.; Chen, Y. Z.J. Chem. Inform. Comp. Sci. 2004, 44, 1630. doi: 10.1021/ci049869h
27. [27]
  (23) Tan, N. X.; Rao, H. B.; Li, Z. R.; Li, X. Y. SAR QSAR Environ. Res. 2009, 20, 27. doi: 10.1080/10629360902724085
28. [28]
  (24) http://www.models.kvl.dk/source/GAPLS/index.asp, accessedJune 2008.
29. [29]
  (25) Leardi, R.; Boggia, R.; Terrile, M. J. Chemom. 1992, 6, 267.
30. [30]
  (26) Leardi, R. J. Chemom. 1994, 8, 65.
31. [31]
  (27) Burbidge, R.; Trotter, M.; Buxton, B.; Holden, S. Comput. Chem. 2001, 26, 5. doi: 10.1016/S0097-8485(01)00094-8
32. [32]
  (28) Cherkassky, V.; Ma, Y. Selection of Meta-parameters forSupport Vector Regression. Proceedings of the InternationalConference on Artificial Neural Networks, Madrid, Spain, Aug28-30, 2002.
33. [33]
  (29) Hao, M.; Li, Y.;Wang, Y.; Zhang, S. Anal. Chim. Acta 2011,690, 53. doi: 10.1016/j.aca.2011.02.004
34. [34]
  (30) Rainville, F. M. D.; Fortin, F. A.; Gardner, M. A.; Parizeau, M.;Gagné, C. DEAP: A Python Framework for EvolutionaryAl rithms. In EvoSoft Workshop, Companion Proc. of theGenetic and Evolutionary Computation Conference, July 07-11,2012.
35. [35]
  (31) Chang, C. C.; Lin, C. J. LIBSVM: A Library for Support VectorMachines, 2001. Software available at http://www.csie.ntu.edu.tw/-cjlin/libsvm, accessed Jun 2008.
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