基于Topomer CoMFA的吡唑啉嘧啶类IL-2诱导T细胞激酶抑制剂的3D-QSAR及分子对接

本文采用Topomer CoMFA方法对37个吡唑啉嘧啶类IL-2诱导T细胞激酶抑制剂进行三维定量构效关系研究.得到3D-QSAR模型,其交互验证系数q~2为0.728,非交叉相关系数r~2为0.994,主成分数N为8,标准估计误差SEE为0.097.结果表明该模型有较好的预测能力.采用Topomer Search技术在ZINC数据库中进行R基的筛选,并设计6个新分子.最后用分子对接技术研究了4个新分子与IL-2诱导的T细胞激酶(Itk)大分子蛋白的作用模式,从结果中可以看到,4个新分子与Itk蛋白的A/LYS391、A/MET438位点作用显著.

3D-QSAR studies of Pyrazolinium IL-2 induces T cell kinase inhibitors based on Topomer CoMFA method and molecular docking

Topomer CoMFA was used to build a three-dimensional quantitative structure-activity relationship(3D-QSAR) model for 37 Pyrazolinium IL-2 induces T cell kinase inhibitors in this paper, The mutual verification coefficient q2 is 0.728, the non-cross correlation coefficient r2 is 0.994, the principal component number N is 8, and the standard estimation error SEE is 0.097. The results show that the model has better predictive ability. The Topomer Search was used to screen the R-based gene in the ZINC database, and 6 new molecules. Finally, by using molecular docking, the action mechanism of 4 new molecules and IL-2 induced T cell kinase (Itk) was studied, and the results showed that the 4 new molecules have significant effects with A/LYS391, and A/MET438 sites of protease.