嘧啶酮类HIV整合酶抑制剂的粗糙集理论构效关系研究
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摘要
利用粗糙集(RS)理论研究了嘧啶酮类HIV整合酶抑制剂(INs)的构效关系(SAR)。首先用量子化学方法得到HIV整合酶抑制剂的量化参数,由量化参数和活性数据构成了粗糙集的信息表;然后通过粗糙集方法,得到核和约简,提取出相应的决策规则,分析药物的构效关系,得出了一系列有意义的结论。研究结果提示整合酶抑制剂的作用机理有可能为是一个双位点作用过程,主要通过N(A4)和OH(A2)形成氢键实现药理作用。本文的结果对研究抗HIV药物的药理、作用机制及整合酶抑制剂的开发均有较强的意义。
The structure-activity relationship study of pyrimidones that are used as HIV integrase inhibitors(INs) was performed with the RS(rough sets) method.An RS process is a concise nonlinear process,and it has broad application foreground in the data mining of nonlinear life courses.In this paper,initially the parameters of HTV integrase inhibitors were computed with the quantum chemistry method,and the information table was constructed from the parameters(condition attributes) and biology activity(decision attributes).Based on the analysis of rough set theory,the core and reduction of attributes set were obtained.Then the decision rules were extracted and the structure-activity relationship was analyzed.From there,a series of useful conclusions were achieved.The results implies that the mechanism of INs may be a two-site action process,which is realized through hydrogen bonds of N(A4) and hydroxyl(A2).
The structure-activity relationship study of pyrimidones that are used as HIV integrase inhibitors(INs) was performed with the RS(rough sets) method.An RS process is a concise nonlinear process,and it has broad application foreground in the data mining of nonlinear life courses.In this paper,initially the parameters of HTV integrase inhibitors were computed with the quantum chemistry method,and the information table was constructed from the parameters(condition attributes) and biology activity(decision attributes).Based on the analysis of rough set theory,the core and reduction of attributes set were obtained.Then the decision rules were extracted and the structure-activity relationship was analyzed.From there,a series of useful conclusions were achieved.The results implies that the mechanism of INs may be a two-site action process,which is realized through hydrogen bonds of N(A4) and hydroxyl(A2).
引文
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2 Makhija M T,Kulkami V M.QSAR of HTV-1 integrase inhibitors by genetic function approximation method.Bioorg Med Chem,2002,10(5):1483-1497.
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6 Douali L,Villemin D and Cherqaouil D.Exploring.QSAR of nonnucleoside reverse transcriptase inhibitors by neural networks:TIBO derivatives.Int J Mol Sci,2004,5:48-55.
14 Pawlak Z.Rough sets theory and its applications to data analysis.Cybernet Syst,1998,29:661-668.
15 Witlox F,Tindemans H.The application of rough sets analysis in activity-based modelling,opportunities and constraints.Expert Syst Appl,2004,27:585-592.
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17 Liu Hao,Qu Lingbo,Gao Hongbin,Wang JinXiang,Han LiPing,Xiang Bingren.Study on the quantitative structure-activity relation-ship of C-10 substituted artemisinin(QHS)'s derivatives using rough set theory.Science in China Series B:Chemistry,2008,51(10):937-945.
18 Cristina Gardelli,Emanuela Nizi,Ester Muraglia,et al.Discovery and synthesis of HTV integrase inhibitors:development of potent and orally bioavailable N-methyl pyrimidones.J.Med.Chem.,2007,50:4953-4975
4 宋晓峰,韩平.最优支持向量机用于HIV-1蛋白酶抑制剂的QSAR建模[J].计算机与应用化学,2007,24(11):1475-1478.
5 宋伟,陈慰祖,张小轶,等.用分子对接方法预测HIV-1整合酶与金精三羧酸抑制剂的相互作用[J].化学物理学报,2003,16(4):257-260.
7 石雅玮.二酮酸类HIV 1整合酶抑制剂的定量构效关系[J].物理化学学报,2007,23(9):1393-1398.
8 高慧,王春芳,高维娜,等.HIV蛋白酶抑制剂的定量构效关系研究及其指导下的修饰[J].原子与分子物理学报,2007,24(4):675-681.
9 仝建波,刘淑玲,刘玉婷,李仲谨,韩玉英,王先锋.三维全息原子场作用矢量用于吡咯类抗艾滋病药物QSAR研究[J].分析科学学报,2008,24(6):275-279.
10 李江波,谢华庆,张敬畅,曹维良.d4T核苷酸类似物抗HIV_1活性的定量构效关系[J].北京化工大学学报,2001,28(1):79-80.
11 堵锡华,冯长君.拓扑集成指数与TIBO类衍生物构效关系的研究[J].计算机与应用化学,2007,24(12):1667-1670.
12 熊远珍,陈芬儿,冯筱晴.DATA类逆转录酶抑制剂的三维定量构效关系[J].化学学报,2006,64(16):1627-1630.
13 刘畅,谭建军,刘明,张小轶,陈慰祖,王存新.计算机辅助设计抗HIV-1整合酶抑制剂的研究进展[J].生物物理学报,2010,26(12):1088-1100.
19 唐建国,谭明术.粗糙集理论中的求核与约简[J].控制与决策,2003,18(7):449-452.
2 Makhija M T,Kulkami V M.QSAR of HTV-1 integrase inhibitors by genetic function approximation method.Bioorg Med Chem,2002,10(5):1483-1497.
3 Alessandra Lumini and Loris Nanni.Machine learning for HTV-1protease cleavage site prediction.Pattern Recognition Letters,2006,27:1537-1544.
6 Douali L,Villemin D and Cherqaouil D.Exploring.QSAR of nonnucleoside reverse transcriptase inhibitors by neural networks:TIBO derivatives.Int J Mol Sci,2004,5:48-55.
14 Pawlak Z.Rough sets theory and its applications to data analysis.Cybernet Syst,1998,29:661-668.
15 Witlox F,Tindemans H.The application of rough sets analysis in activity-based modelling,opportunities and constraints.Expert Syst Appl,2004,27:585-592.
16 Pawlak Z.Rough sets and intelligent data analysis.Information Sciences,2002,147(1-4):1-12.
17 Liu Hao,Qu Lingbo,Gao Hongbin,Wang JinXiang,Han LiPing,Xiang Bingren.Study on the quantitative structure-activity relation-ship of C-10 substituted artemisinin(QHS)'s derivatives using rough set theory.Science in China Series B:Chemistry,2008,51(10):937-945.
18 Cristina Gardelli,Emanuela Nizi,Ester Muraglia,et al.Discovery and synthesis of HTV integrase inhibitors:development of potent and orally bioavailable N-methyl pyrimidones.J.Med.Chem.,2007,50:4953-4975
4 宋晓峰,韩平.最优支持向量机用于HIV-1蛋白酶抑制剂的QSAR建模[J].计算机与应用化学,2007,24(11):1475-1478.
5 宋伟,陈慰祖,张小轶,等.用分子对接方法预测HIV-1整合酶与金精三羧酸抑制剂的相互作用[J].化学物理学报,2003,16(4):257-260.
7 石雅玮.二酮酸类HIV 1整合酶抑制剂的定量构效关系[J].物理化学学报,2007,23(9):1393-1398.
8 高慧,王春芳,高维娜,等.HIV蛋白酶抑制剂的定量构效关系研究及其指导下的修饰[J].原子与分子物理学报,2007,24(4):675-681.
9 仝建波,刘淑玲,刘玉婷,李仲谨,韩玉英,王先锋.三维全息原子场作用矢量用于吡咯类抗艾滋病药物QSAR研究[J].分析科学学报,2008,24(6):275-279.
10 李江波,谢华庆,张敬畅,曹维良.d4T核苷酸类似物抗HIV_1活性的定量构效关系[J].北京化工大学学报,2001,28(1):79-80.
11 堵锡华,冯长君.拓扑集成指数与TIBO类衍生物构效关系的研究[J].计算机与应用化学,2007,24(12):1667-1670.
12 熊远珍,陈芬儿,冯筱晴.DATA类逆转录酶抑制剂的三维定量构效关系[J].化学学报,2006,64(16):1627-1630.
13 刘畅,谭建军,刘明,张小轶,陈慰祖,王存新.计算机辅助设计抗HIV-1整合酶抑制剂的研究进展[J].生物物理学报,2010,26(12):1088-1100.
19 唐建国,谭明术.粗糙集理论中的求核与约简[J].控制与决策,2003,18(7):449-452.