Bioinformatics Center, Northwest A&F University, Yangling, Shaanxi 712100,China.
J Mol Graph Model. 2011 Sep;30:67-81. doi: 10.1016/j.jmgm.2011.06.006. Epub 2011 Jun 25.
CDK₂ (cyclin-dependent kinase 2) is an attractive target for therapeutic intervention in cancer. In this work, quantitative structure-activity relationship (QSAR), molecular docking, and molecular dynamics (MD) studies were performed on three sets of 155 CDK₂ inhibitors. The obtained models exhibit good predictive capability in both internal and external validations (q²=0.73, r²(pred)=0.94 for 6, 6-dimethyl pyrrolo [3,4-c]pyrazoles analogs, q²=0.62, r²(pred)=0.63 for imidazole pyrimidine amides analogs and q²=0.56, r²(pred)=0.58 for 4-(pyrazol-4-yl)-pyrimidines analogs). Furthermore, a comparison between 3D-contour map, docking and MD simulation explore in detail the binding modes and the key structural features impacting the interaction of each series of inhibitors with the CDK₂ enzyme, which should be useful to aid the designing of new inhibitors with CDK₂ improved biological response.
CDK₂（细胞周期蛋白依赖性激酶 2）是癌症治疗干预的一个有吸引力的靶点。在这项工作中，对三组 155 种 CDK₂抑制剂进行了定量构效关系（QSAR）、分子对接和分子动力学（MD）研究。所得到的模型在内部和外部验证中都表现出良好的预测能力（6,6-二甲基吡咯并[3,4-c]吡唑类似物的 q²=0.73，r²（pred）=0.94，咪唑嘧啶酰胺类似物的 q²=0.62，r²（pred）=0.63，4-（吡唑-4-基）嘧啶类似物的 q²=0.56，r²（pred）=0.58）。此外，3D 等高线图、对接和 MD 模拟之间的比较详细探讨了每个系列抑制剂与 CDK₂酶相互作用的结合模式和关键结构特征，这对于设计具有改善的 CDK₂生物学反应的新型抑制剂应该是有用的。
