摘要
通过一系列肌钙蛋白Ⅰ相关激酶抑制剂苯磺酰胺衍生物构建了其3D-QSAR模型,研究其结构与活性关系。所得CoMFA、TopomerCoMFA模型的交叉验证相关系数q2分别为0.622、0.768,非交叉验证系数r2分别为0.952、0.981,外部验证相关系数R2pred分别为0.823、0.754,说明模型具有良好的预测性能和稳定性。采用Topomer Search对ZINC数据库进行虚拟筛选,共得到25个分子,其预测活性均高于活性最高的模板分子。最后通过分子对接筛选得到11个分子可作为TNNI3K抑制剂进一步研究。
Three dimensional structure-activity relationships（3 D-QSAR）models were constructed with a series of Troponin I-interacting protein Kinase inhibitors benzyl sulfonamide derivatives to investigate the structure-activity relationship. The cross-validate regress coefficients（q2）of CoMFA and TopomerCoMFA were0.622,0.768,and the noncross-validate regress coefficients（r2）were 0.952,0.981,respectively. However,theexternal validation coefficients（r2 pred） of CoMFA and TopomerCoMFA were 0.823, 0.754 respectively,indicating that both models are favorable stable and predictable. Moreover,Topomer Search was utilized forvirtual screening in ZINC database,and 25 new molecules were obtained,which exhibited higher activitycompared with those template molecules. Finally,11 molecules were screened by molecular docking as the potential inhibitors of TNNI3 K.
作者
徐闻曦
蔡晓然
郑小娇
刘根炎
巨修练
XU Wenxi;CAI Xiaoran;ZHENG Xiaojiao;LIU Genyan;JU Xiulian(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China)
出处
《武汉工程大学学报》
CAS
2018年第5期485-493,共9页
Journal of Wuhan Institute of Technology
