嘧啶酮类HIV整合酶抑制剂的粗糙集理论构效关系研究

The application of rough sets in SAR analysis of pyrimidones as HIV integrase inhibitors

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 HIV 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 ofN （A4） and hydroxyl （A2）.