物理化学学报 >> 2003, Vol. 19 >> Issue (08): 695-700.doi: 10.3866/PKU.WHXB20030804

研究论文 上一篇    下一篇

基于遗传算法的PTP1B抑制剂的二维定量构效关系研究

潘咏梅;计明娟   

  1. 中国科学院研究生院,北京　100039
  • 收稿日期:2003-01-13 修回日期:2003-03-13 发布日期:2003-08-15
  • 通讯作者: 计明娟 E-mail:jmj@gscac.ac.cn

Applications of Genetic Algorithms on 2D-QSAR Analysis of Benzofuran and Benzothiophene Biphenyls as PTP1B Inhibitors

Pan Yong-Mei;Ji Ming-Juan   

  1. Graduate School of Chinese Academy of Sciences, Beijing　100039
  • Received:2003-01-13 Revised:2003-03-13 Published:2003-08-15
  • Contact: Ji Ming-Juan E-mail:jmj@gscac.ac.cn

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摘要： 利用遗传算法,并结合线性回归和交叉验证方法,对一系列43个苯并呋喃/噻吩联二苯类PTP1B抑制剂作了二维定量构效关系的研究.计算得到了一组效果较好的定量构效关系模型.模型不仅具有好的回归能力,而且还具有很好的预测能力.同时,通过分析在遗传优化过程中参数在精华种群中所占的比例,还得到了可能对活性影响较大的成分.计算结果表明,分子的4个参数:lgP(分配系数)、Area（表面积）、MW（分子量）以及Dip（偶极距）是影响化合物活性的最重要的参数,这对抑制剂的设计和改造提供了指导.

关键词: 二维定量构效关系, 遗传算法, PTP1B抑制剂

Abstract: Quantitative structure-activity relationships (QSARs) for 43 benzofuran and benzothiophene biphenyls were studied. By using a genetic algorithm (GA), a group of multiple regression models with high fitness scores (r2 was up to 0.70) were generated. From the statistical analyses of the descriptors used in the evolution procedure, four of them, including the partition coefficient (lgP), the molecular surface area (Area), the molecular weight (MW), and the dipole vector (Dip) were found to be the principal features affecting the biological activity. For example, the molecular surface area appeared in 94％ of the models in the elite populations. That is to say, the hydrophobic interactions between the inhibitors and the receptors are very important to the biological activity, which supplies a guide for the design and reconstruction of new PTP1B inhibitors.

Key words: 2D-QSAR, Genetic algorithm, PTP1B inhibitors