Citation:
HE Bing, LUO Yong, LI Bing-Ke, XUE Ying, YU Luo-Ting, QIU Xiao-Long, YANG Teng-Kuei. Predicting and Virtually Screening Breast Cancer Targeting Protein HEC1 Inhibitors by Molecular Descriptors and Machine Learning Methods[J]. Acta Physico-Chimica Sinica,
;2015, 31(9): 1795-1802.
doi:
10.3866/PKU.WHXB201507301
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Highly expressed in cancer 1 (HEC1) is a conserved mitotic regulator that is critical for spindle checkpoint control, kinetochore functionality, and cell survival. Overexpression of HEC1 has been detected in a variety of human cancers, and it is linked to poor prognosis of primary breast cancers. Thus, it is important to screen novel inhibitors with high affinity for HEC1. Machine learning (ML) methods were exhibiting od pharmacodynamics, and toxicity. In this work, two ML methods, support vector machines (SVMs) and random forests (RFs), were used to develop a classification method for searching inhibitors and non-inhibitors of HEC1 from the chemical library of structural diversity by screening characteristics of molecular descriptors. Both ML methods achieved promising prediction accuracies, and the RF model showed better performance. We performed virtual screening of HEC1 inhibitors by the RF model from an in-house database to screen potential HEC1 inhibitors. Two novel potential candidates were found. In vitro experiments of the two compounds showed that both had a certain degree of antitumor activity for the MDA-MB-468 and MDA-MB-231 breast cancer cell lines. Our study shows that ML methods are promising to design and virtually screen inhibitors of HEC1.
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-
[1]
(1) Gan, S. J.; Wang, Q.; Zhu, L. M.; Xie, H.; Ding, X. F. Basic & Clin. Med. 2015, 35 (1), 134. [甘绍举, 王青, 朱丽敏, 谢浩, 丁先锋. 基础医学与临床, 2015, 35 (1), 134.]
-
[2]
(2) Chen, Y.; Riley, D. J.; Chen, P. L.; Lee, W. H. Mol. Cell Biol. 1997, 17 (10), 6049.
-
[3]
(3) Du, X. L.; Wang, M. R. Acta Acad. Med. Sin. 2007, 29 (1), 137. [杜小莉, 王明荣. 中国医学科学院学报, 2007, 29 (1), 137.]
-
[4]
(4) Hu, C. M.; Zhu, J.; Guo, X. E.; Chen, W.; Qiu, X. L.; N , B.; Chien, R.; Wang, Y. V.; Tsai, C. Y.; Wu, G.; Kim, Y.; Lopez, R.; Chamberlin, A. R.; Lee, E. H.; Lee, W. H. Oncogene 2015, 34, 1220. doi: 10.1038/onc.2014.67
-
[5]
(5) Huang, L. Y.; Chang, C. C.; Lee, Y. S.; Chang, J. M.; Huang, J. J.; Chuang, S. H.; Kao, K. J.; Lau, G. M.; Tsai, P. Y.; Liu, C. W.; Lin, H. S.; Lau, J. Y. Mol. Cancer Ther. 2014, 13 (6), 1419.
-
[6]
(6) Lee, Y. S.; Chuang, S. H.; Huang, L. Y.; Lai, C. L.; Lin, Y. H.; Yang, J. Y.; Liu, C. W.; Yang, S. C.; Lin, H. S.; Chang, C. C.; Lai, J. Y.; Jian, P. S.; Lam, K.; Chang, J. M.; Lau, J. Y.; Huang, J. J. J. Med. Chem. 2014, 57 (10), 4098. doi: 10.1021/jm401990s
-
[7]
(7) Wu, G.; Qiu, X. L.; Zhou, L.; Zhu, J.; Chamberlin, R.; Lau, J.; Chen, P. L.; Lee, W. H. Cancer Res. 2008, 68 (20), 8393. doi: 10.1158/0008-5472.CAN-08-1915
-
[8]
(8) Qiu, X. L.; Li, G.; Wu, G.; Zhu, J.; Zhou, L.; Chen, P. L.; Chamberlin, A. R.; Lee, W. H. J. Med. Chem. 2009, 52 (6), 1757. doi: 10.1021/jm8015969
-
[9]
(9) Chen, Y.; Riley, D. J.; Zheng, L.; Chen, P. L.; Lee, W. H. J. Biol. Chem. 2002, 277 (51), 49408. doi: 10.1074/jbc.M207069200
-
[10]
(10) Diaz-Rodríguez, E.; Sotillo, R.; Schvartzman, J. M.; Benezra, R. Proc. Natl. Acad. Sci. U. S. A. 2008, 105 (43), 16719. doi: 10.1073/pnas.0803504105
-
[11]
(11) Ferretti, C.; Totta, P.; Fiore, M.; Mattiuzzo, M.; Schillaci, T.; Ricordye, R.; Di Leonardo, A.; Degrassi, F. Cell Cycle 2010, 9 (20), 4174. doi: 10.4161/cc.9.20.13457
-
[12]
(12) Wei, R.; N , B.; Wu, G.; Lee, W. H. Mol. Biol. Cell 2011, 22 (19), 3584. doi: 10.1091/mbc.E11-01-0012
-
[13]
(13) Xue, Y.; Li, H.; Ung, C.; Yap, C.; Chen, Y. Chem. Res. Toxicol. 2006, 19, 1030. doi: 10.1021/tx0600550
-
[14]
(14) Xue, Y.; Yap, C. W.; Sun, L. Z.; Cao, Z. W.; Wang, J.; Chen, Y. Z. J. Chem. Inf. Comput. Sci. 2004, 44, 1497. doi: 10.1021/ci049971e
-
[15]
(15) Xue, Y.; Li, Z.; Yap, C. W.; Sun, L.; Chen, X.; Chen, Y. Z. J. Chem. Inf. Comput. Sci. 2004, 44, 1630. doi: 10.1021/ci049869h
-
[16]
(16) Yang, X. G.; Chen, D.; Wang, M.; Xue, Y.; Chen, Y. Z. J. Comput. Chem. 2009, 30, 1202. doi: 10.1002/jcc.v30:8
-
[17]
(17) Yang, X. G.; Lv, W.; Chen, Y. Z.; Xue, Y. J. Comput. Chem. 2010, 31, 1249.
-
[18]
(18) Lv, W.; Xue, Y. Eur. J. Med. Chem. 2010, 45, 1167. doi: 10.1016/j.ejmech.2009.12.038
-
[19]
(19) Cong, Y.; Yang, X.; Lv, W.; Xue, Y. J. Mol. Graph. Model. 2009, 28, 236. doi: 10.1016/j.jmgm.2009.08.001
-
[20]
(20) Luan, F.; Liu, H.; Ma, W.; Fan, B. Eur. Med. Chem. 2008, 43, 43. doi: 10.1016/j.ejmech.2007.03.002
-
[21]
(21) Ung, C. Y.; Li, H.; Yap, C. W.; Chen, Y. Z. Mol. Pharmacol. 2007, 71, 158.
-
[22]
(22) Li, H.; Ung, C.; Yap, C.; Xue, Y.; Li, Z.; Cao, Z.; Chen, Y. Chem. Res. Toxicol. 2005, 18, 1071. doi: 10.1021/tx049652h
-
[23]
(23) Li, B. K.; Cong, Y.; Tian, Z. Y.; Xue, Y. Acta Phys. -Chim. Sin. 2014, 30 (1), 171. [李秉轲, 丛湧, 田之悦, 薛英. 物理化学学报, 2014, 30 (1), 171.] doi: 10.3866/PKU.WHXB201311041
-
[24]
(24) Huang, J. J.; Lau, J. Improved Modulators of HEC1 Activity and Methods. CN Patent 103038231.A, 2013-04-10. [Huang, J. J., Lau, J. HEC1活性调节剂及其方法: 中国, CN103038231.A[P]. 2013-04-10.]
-
[25]
(25) Duda, R. O.; Hart, P. E. Pattern Classification and Scene Analysis; John Wiley & Sons: Hoboken, New Jersey, USA, 1973.
-
[26]
(26) ChemDraw 7.0.1 ed.; CambridgeSoft Corporation, Cambridge: Massachusetts, USA, 2007.
-
[27]
(27) Corina 3.4 edn.; Molecular Networks GmbH Computerchemie: Erlangen, Germany, 2006.
-
[28]
(28) Burges, C. J. Data Min. Knowl. Disc. 1998, 2, 121.
-
[29]
(29) Vapnik, V. N. The Nature of Statistical Learning Theory; Springer: Berlin & Heidelberg, Germany, 1995.
-
[30]
(30) Doucet, J. P.; Barbault, F.; Xia, H.; Panaye, A.; Fan, B. Curr. Comput-Aid. Drug. 2007, 3, 263. doi: 10.2174/157340907782799372
-
[31]
(31) Svetnik, V.; Liaw, A.; Tong, C.; Culberson, J. C.; Sheridan, R. P.; Feuston, B. P. J. Chem. Inf. Comput. Sci. 2003, 43, 1947. doi: 10.1021/ci034160g
-
[32]
(32) Breiman, L. Mach. Learn. 2001, 45, 5. doi: 10.1023/A: 1010933404324
-
[33]
(33) Khandelwal, A.; Krasowski, M. D.; Reschly, E. J.; Sinz, M. W.; Swaan, P. W.; Ekins, S. Chem. Res. Toxicol. 2008, 21, 1457. doi: 10.1021/tx800102e
-
[34]
(34) Breiman, L. Out-of-bag Estimation, 1996, http://citeseerx.ist.psu.edu.sci-hub.org/viewdoc/download?doi=10.1.1.45.3712&rep=rep1&type=pdf (accessed Mar 15, 2015).
-
[35]
(35) Breiman, L. Wald Lecture II, Looking inside the Black Box, 2005. http://www.stat.berkeley.edu/users/breiman (accessed Mar 15, 2015).
-
[36]
(36) Breiman, L.; Cutler, A. Random Forests, Version 5.1, 2004. http://www.stat.berkeley.edu/~breiman/RandomForests/cc_home.htm (accessed Mar 15, 2015).
-
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