细胞周期蛋白依赖激酶
细胞周期蛋白依赖激酶2
对接(动物)
计算生物学
激酶
生物化学
化学
生物
生物物理学
细胞周期
蛋白激酶A
细胞
医学
护理部
作者
Lei Zheng,Yunpeng Yang,Jingxiao Bao,Liping He,Yue Qi,John Z. H. Zhang
摘要
Cyclin-dependent kinase (CDK) is a serine/threonine protein kinase family that cooperates with cyclin and plays an important role in the regulation of cell cycle. Cyclin-dependent kinase 2 is an important member of the CDK family and holds great promise as an anti-cancer drug target. In this study, we used molecular docking and physics-based binding free energy calculation method AS-IE that explicitly calculated protein-ligand binding entropy to discover novel inhibitors of CDK2. A total of 17 inhibitors were discovered with the best IC50 reaching ~2 μM. Decomposition of the binding free energy using AS-IE reveals key protein-ligand interactions that determines the activity. These results provided a good example of drug design using physics-based free energy calculation method such as AS-IE and the novel compounds offered a good start point for further development of CDK2 inhibitors.
科研通智能强力驱动
Strongly Powered by AbleSci AI