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.
1. [1]
  Jiageng Li , Putrama . 数值积分耦合非线性最小二乘法一步确定反应动力学参数. University Chemistry, 2025, 40(6): 364-370. doi: 10.12461/PKU.DXHX202407098
2. [2]
  Yihui Song , Shangshang Qin , Kai Wu , Chengyun Jin , Bin Yu . 生物化学在高水平创新型药学人才培养中的交叉融合应用——以去甲基化酶LSD1抑制剂的活性评价为例. University Chemistry, 2025, 40(6): 341-352. doi: 10.12461/PKU.DXHX202406018
3. [3]
  Liwei Wang , Guangran Ma , Li Wang , Fugang Xu . A Comprehensive Analytical Chemistry Experiment: Colorimetric Detection of Vitamin C Using Nanozyme and Smartphone. University Chemistry, 2024, 39(8): 255-262. doi: 10.3866/PKU.DXHX202312094
4. [4]
  Meijin Li , Xirong Fu , Xue Zheng , Yuhan Liu , Bao Li . The Marvel of NAD⁺: Nicotinamide Adenine Dinucleotide. University Chemistry, 2024, 39(9): 35-39. doi: 10.12461/PKU.DXHX202401027
5. [5]
  Xiaoli Sun , Xiang Wu , Li Gan , Wenming Wan . Barbier Polymerization: A New Teaching Case for Step-Growth Polymerization. University Chemistry, 2025, 40(4): 113-118. doi: 10.12461/PKU.DXHX202406102
6. [6]
  Ran HUO , Zhaohui ZHANG , Xi SU , Long CHEN . Research progress on multivariate two dimensional conjugated metal organic frameworks. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2063-2074. doi: 10.11862/CJIC.20240195
7. [7]
  Lewang Yuan , Yaoyao Peng , Zong-Jie Guan , Yu Fang . 二维共价有机框架作为光催化剂在有机合成中的研究进展. Acta Physico-Chimica Sinica, 2025, 41(8): 100086-. doi: 10.1016/j.actphy.2025.100086
8. [8]
  Jingjing QING , Fan HE , Zhihui LIU , Shuaipeng HOU , Ya LIU , Yifan JIANG , Mengting TAN , Lifang HE , Fuxing ZHANG , Xiaoming ZHU . Synthesis, structure, and anticancer activity of two complexes of dimethylglyoxime organotin. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1301-1308. doi: 10.11862/CJIC.20240003
9. [9]
  Xiaoling LUO , Pintian ZOU , Xiaoyan WANG , Zheng LIU , Xiangfei KONG , Qun TANG , Sheng WANG . Synthesis, crystal structures, and properties of lanthanide metal-organic frameworks based on 2, 5-dibromoterephthalic acid ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1143-1150. doi: 10.11862/CJIC.20230271
10. [10]
  Jianding LI , Junyang FENG , Huimin REN , Gang LI . Proton conductive properties of a Hf(Ⅳ)-based metal-organic framework built by 2,5-dibromophenyl-4,6-dicarboxylic acid. Chinese Journal of Inorganic Chemistry, 2025, 41(6): 1094-1100. doi: 10.11862/CJIC.20240464
11. [11]
  Bao Jia , Yunzhe Ke , Shiyue Sun , Dongxue Yu , Ying Liu , Shuaishuai Ding . Innovative Experimental Teaching for the Preparation and Modification of Conductive Organic Polymer Thin Films in Undergraduate Courses. University Chemistry, 2024, 39(10): 271-282. doi: 10.12461/PKU.DXHX202404121
12. [12]
  Yinwu Su , Xuanwen Zheng , Jianghui Du , Boda Li , Tao Wang , Zhiyan Huang . Green Synthesis of 1,3-Dibromoacetone Using Halogen Exchange Method: Recommending a Basic Organic Synthesis Teaching Experiment. University Chemistry, 2024, 39(5): 307-314. doi: 10.3866/PKU.DXHX202311092
13. [13]
  Yongzhi LI , Han ZHANG , Gangding WANG , Yanwei SUI , Lei HOU , Yaoyu WANG . A two-dimensional metal-organic framework for the determination of nitrofurantoin and nitrofurazone in aqueous solution. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 245-253. doi: 10.11862/CJIC.20240307
14. [14]
  Shiyang He , Dandan Chu , Zhixin Pang , Yuhang Du , Jiayi Wang , Yuhong Chen , Yumeng Su , Jianhua Qin , Xiangrong Pan , Zhan Zhou , Jingguo Li , Lufang Ma , Chaoliang Tan . 铂单原子功能化的二维Al-TCPP金属-有机框架纳米片用于增强光动力抗菌治疗. Acta Physico-Chimica Sinica, 2025, 41(5): 100046-. doi: 10.1016/j.actphy.2025.100046
15. [15]
  Xinxin YU , Yongxing LIU , Xiaohong YI , Miao CHANG , Fei WANG , Peng WANG , Chongchen WANG . Photocatalytic peroxydisulfate activation for degrading organic pollutants over the zero-valent iron recovered from subway tunnels. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 864-876. doi: 10.11862/CJIC.20240438
16. [16]
  Yaofeng Yuan , Keyin Ye , Chunfa Xu , Hong Yan , Yuanming Li . Fostering an International Perspective in Postgraduate Student Teaching: A Case Study of the Organic Structure Analysis Course. University Chemistry, 2024, 39(6): 145-150. doi: 10.3866/PKU.DXHX202402024
17. [17]
  Wei Li , Jinfan Xu , Yongjun Zhang , Ying Guan . 共价有机框架整体材料的制备及食品安全非靶向筛查应用——推荐一个仪器分析综合化学实验. University Chemistry, 2025, 40(6): 276-285. doi: 10.12461/PKU.DXHX202406013
18. [18]
  Youlin SI , Shuquan SUN , Junsong YANG , Zijun BIE , Yan CHEN , Li LUO . Synthesis and adsorption properties of Zn(Ⅱ) metal-organic framework based on 3, 3', 5, 5'-tetraimidazolyl biphenyl ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1755-1762. doi: 10.11862/CJIC.20240061
19. [19]
  Jie ZHAO , Huili ZHANG , Xiaoqing LU , Zhaojie WANG . Theoretical calculations of CO₂ capture and separation by functional groups modified 2D covalent organic framework. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 275-283. doi: 10.11862/CJIC.20240213
20. [20]
  Shengbiao Zheng , Liang Li , Nini Zhang , Ruimin Bao , Ruizhang Hu , Jing Tang . Metal-Organic Framework-Derived Materials Modified Electrode for Electrochemical Sensing of Tert-Butylhydroquinone: A Recommended Comprehensive Chemistry Experiment for Translating Research Results. University Chemistry, 2024, 39(7): 345-353. doi: 10.3866/PKU.DXHX202310096

Get Citation

PDF

XML

Metrics

PDF Downloads(947)
Abstract views(974)
HTML views(12)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142