DNA依赖蛋白激酶抑制剂的CoMFA研究

QSAR study of a series of the DNA-dependent protein kinase inhibitors by CoMFA

运用比较分子力场分析方法(CoMFA),以DNA依赖蛋白激酶(DNA-PK)抑制剂分子为研究对象,建立1组对DNA依赖蛋白激酶有抑制活性化合物的三维定量构效关系(3D-QSAR)模型,探索其活性数据和三维结构参数的关系,所建最佳模型交叉验证相关系数q^2=0.670,非交叉验证相关系数R^2=0.993,标准偏差SD=0.053,说明该模型预测能力较好。根据CoMFA模型的三维等势图可知,小体积、电负性大的取代基团,能提高该类化合物的活性,为新型DNA-PK抑制剂分子的设计提供了理论依据。

To study the relationship between the bioactivity and structure parameters of a series of DNA-dependent protein kinase inhibitors, a 3D-QSAR （Three Dimensional Quantitative Structure-Activity Relationship） model was established by using comparative molecular field analysis （CoMFA） method in the present paper. The cross-validated coefficient q2was 0.670, the non-cross-validated R2 was 0.993, the standard deviation was 0.053. The contributions of steric and electrostatic fields to bioactivity are 52.3% and 47.7% respectively. Results showed the model established has good predictive ability. Reducing the bulk of substituent or increasing negative charge of substituent can increase the bioactivity, and thus provide a theoretical basis for the design of new DNA-PK inhibitors molecules.