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用支持向量机预测HIV-1整合酶抑制剂活性

刘昕, 谭建军, 陈慰祖, 刘斌, 李杉, 王存新

刘昕, 谭建军, 陈慰祖, 刘斌, 李杉, 王存新. 用支持向量机预测HIV-1整合酶抑制剂活性[J]. 北京工业大学学报, 2013, 39(4): 634-640.
引用本文: 刘昕, 谭建军, 陈慰祖, 刘斌, 李杉, 王存新. 用支持向量机预测HIV-1整合酶抑制剂活性[J]. 北京工业大学学报, 2013, 39(4): 634-640.
LIU Xin, TAN Jian-jun, CHEN Wei-zu, LIU Bin, LI Shan, WANG Cun-xin. Support Vector Machine Applied to Predicting the Activity of HIV-1 IN Inhibitors[J]. Journal of Beijing University of Technology, 2013, 39(4): 634-640.
Citation: LIU Xin, TAN Jian-jun, CHEN Wei-zu, LIU Bin, LI Shan, WANG Cun-xin. Support Vector Machine Applied to Predicting the Activity of HIV-1 IN Inhibitors[J]. Journal of Beijing University of Technology, 2013, 39(4): 634-640.

用支持向量机预测HIV-1整合酶抑制剂活性

基金项目: 

国家自然科学基金资助项目(21173014)

科技部国际合作项目(2010DFA31710)

详细信息
    作者简介:

    刘昕(1974-),女,讲师,主要从事分子设计和蛋白质组学方面的研究;E-mail:dbliuxin@bjut.edu.cn

    通讯作者:

    王存新(1943-)

  • 中图分类号: R914.2

Support Vector Machine Applied to Predicting the Activity of HIV-1 IN Inhibitors

  • 摘要: HIV整合酶可催化病毒复制周期中的整合过程,即将HIV反转录产物cDNA整合入宿主基因组,它是病毒复制过程中不可缺少的酶,也是抗HIV药物设计的重要靶点.构建嘧啶酮类(pyrimidones)HIV-1整合酶抑制剂定量构效关系模型,有助于进一步了解影响抑制剂活性的结构因素.本文应用CoMFA软件计算了68个化合物的拓扑、分子极化、亲水性等结构参数,用所选的结构参数作为支持向量机(support vector machine,SVM)的输入,建立起非线性的支持向量机回归模型.研究表明:支持向量机算法与分子结构参数的有机集成,可为HIV整合酶抑制剂的结构与活性数据建立起预测模型,为抗HIV药物设计提供生物学信息.
    Abstract: HIV integrase(IN) catalyzes the integration process in the viral life cycle.IN helps the viral reverse transcription product cDNA integrating into the host chromosome.As an indispensable enzyme,IN is also an important target for designing and developing the novel anti-HIV drugs.Constructing the QSAR model of the HIV-1 IN pyrimidones inhibitors can help for understanding of the structural factors.In this paper,the CoMFA software was used to calculate topological descriptors,polarizable descriptors and hydrophilic descriptors and other structural parameters for 68 compounds.The structural parameters were selected as inputs of support vector machine(SVM) to establish the non-linear regression model.Resultsshow that the SVM algorithm combined with QSAR can establish the forecasting model for inhibitors,and provide biological information for the design of anti-HIV drugs.
  • [1]

    POMMIER Y,JOHNSON A A,MARCHAND C.Integraseinhibitors to treat HIV/AIDS[J].Nat Rev Drug Discov,2005,4(3):236-248.

    [2] 姜晓华,龙亚秋.结构多样的HIV-1整合酶抑制剂:过去、现在和未来[J].有机化学,2004(24):1380-1388.JIANG Xiao-hua,LONG Ya-qiu.Structurally diverse HIV-1integrase inhibitors:past,present and perspective[J].Chin J Org Chem,2004(24):1380-1388.(in Chinese)
    [3]

    DAYAM R,SANCHEZ T,CLEMENT O,et al.β-Diketoacid pharmacophore hypothesis:1.discovery of a novelclass of HIV-1 integrase inhibitors[J].J Med Chem,2005,48(1):111-120.

    [4]

    HAZUDA D J,PETER F,MARC W,et al.Inhibitors ofstrand transfer that prevent integration and inhibit HIV-1replicatoion in cells[J].Science,2000,287(5453):646-650.

    [5]

    EGBERTSONM S.HIV integrase inhibitors:fromdiketoacids to heterocyclic templates:a history of HIVintegrase medicinal chemistry at merck west point andmerck rome(IRBM)[J].Current Topics in MedicinalChemistry,2007,7(13):1251-1272.

    [6]

    STEIGBIGEL R,KUMARP,ERON J,et al.Results ofBENCHMRK-2,a phaseⅢstudy evaluating the efficacyand safety of MK-0518,a novel HIV-1 integraseinhibitor,in patients with triple-class resistant virus[C]∥14th Conference on Retroviruses and OpportunisticInfections,Los Angeles,February 25-28,2007.

    [7]

    VAPNIK V.The nature of statistical learning theory[M].New York:Springer-Verlag,1995.

    [8]

    HUA S,SUN Z.A novel method of protein secondary structure prediction with high segment overlap measure:support vector machine approach[J].J Mol Biol,2001,308(2):397-407.

    [9]

    BURBIDGE R,TROTTER M,BUXTON B,et al.Drug design by machine learning:support vector machines for pharmaceutical data analysis[J].Computers and Chemistry,2001,26(1):5-14.

    [10]

    HONG S J,WEISS S M.Advances in predictive models for data mining[J].Pattern Recognition Letters,2001,22:55-61.

    [11]

    GAOA J B,GUNNB S R,HARRISB C J.SVM regression through variational methods and its sequential implementation[J].Neurocomputing,2003,55(1):151-167.

    [12] 金宏.统计模拟肽及蛋白质的性质和活性[D].浙江大学化学系,2010.JIN Hong.Statisitcal modeling of the property and activity of pePtides and proteins[D].Hangzhou:Department of Chemistry,Zhejiang University,2010.(in Chinese)[13]CORTES C,VAPNIK V.Support vector networks[J].Machine Learning,1995,20(3):273-293.
    [14] 梅虎,梁桂兆,周原,等,支持向量机用于定量构效关系建模的研究[J].科学通报,2005,50(16):1703-1708.MEI Hu,LIANG Gui-zhao,ZHOU Yuan,et al.Modeling research on quantitative structure and activity relationship using support vector machine[J].Chinese Science Bulletin,2005,50(16):1703-1708.(in Chinese)
    [15]

    FLACH P A.On the state of the art in machine learning:a personal review[J].Artificial Intelligence,2001,131(1):199-222.

    [16]

    BELOUSOV A I,VERZAKOV S A,FRESE J V.A flexible classification approach with optimal generalization performance:support vector machines[J].Chemom Intell Lab Syst,2002,64(1):15-25.

    [17] 纪彩虹.定量构效关系的原理、方法及其研究进展[J].甘肃联合大学学报:自然科学版,2011.25(2):58-62.JI Cai-hong.The principle,methods,realization process and research status of QSAR/QSPR[J].Journal of Gansu Lianhe University:Natural Science Edition,2011,25(2):58-62.(in Chinese)
    [18] 冯丽萍,郭正元,梁菁,等.几种QSAR建模方法的研究进展与应用[J].农业环境科学学报,2007,26(增刊):651-655.FENG Li-ping,GUO Zheng-yuan,LIANG Jing,et al.Research progress and application in the several QSAR modeling method[J].Journal of Agro-Environment Science,2007,26(S):651-655.(in Chinese)
    [19]

    CRISTINA G,EMANUELA N,ESTER M,et al.Discovery and synthesis of HIV integrase inhibitors:development of potent and orally bioavailable N-Methly pyrimidones[J].J Med Chem,2007(50):4953-4975.

    [20]

    ESTER M,OLAF K,CRISTINA G,et al.Design and synthesis of bicyclic pyrimidinones as potent and orally bioavailable HIV-1integrase inhibitors[J].J Med Chem,2008(51):861-874.

    [21]

    JING S,HAI F C,HAI R X,et al.Comparative study of factor Xa inhibitors using molecular docking/SVM/HQSAR/3D-QSAR methods[J].QSAR Comb Sci,25,2006(1):25-45.

    [22]

    MARCHAND C,JOHNSON A A,SEMENOVA E,et al.Mechanisms and inhibition of HIV integration[J].Drug Discovery Today:Disease Mechanisms,2006(3):253-260.

    [23] 郭涤亮,刘冠男,周宇,等.HIV整合酶抑制剂的研究进展[J].有机化学,2010,30(4):477-485.GUO Di-liang,LIU Guan-nan,ZHOU Yu,et al.Research progress in HIV integrase inhibitors[J].Chinese Journal of Organic Chemistry,2010,30(4):477-485.(in Chinese)
    [24]

    SATO M,MOTOMURA T,ARAMAKI H,et al.Novel HIV-1integrase inhibitors derived from quinolone antibiotics[J].J Med Chem,2006(49):15061508.

    [25]

    PACE P,SPIESER S A H,SUMMA V.4-Hydroxy-5-pyrrolinone-3-carboxamide HIV-1Integrase Inhibitors[J].Bioorganic&Medicinal Chemistry Letters,2008,18(14):3865-3869.

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  • 被引次数: 0
出版历程
  • 收稿日期:  2011-12-06
  • 网络出版日期:  2022-11-13

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