铰链
配体(生物化学)
激酶
氢键
化学
计算生物学
合理设计
组合化学
结合位点
细胞周期蛋白依赖激酶9
蛋白激酶A
立体化学
生物物理学
生物化学
丝裂原活化蛋白激酶激酶
生物
受体
遗传学
分子
物理
有机化学
经典力学
作者
Zheng Zhao,Philip E. Bourne
标识
DOI:10.1021/acsmedchemlett.3c00212
摘要
ATP-competitive kinase inhibitors form hydrogen bond interactions with the kinase hinge region at the adenine binding site. Thus, it is crucial to explore hinge-ligand recognition as part of a rational drug design strategy. Here, harnessing known ligand-bound kinase structures and experimental assay resources, we first created a kinase structure-assay database (KSAD) containing 2705 nM ligand-bound kinase complexes. Then, using KSAD, we systematically investigate hinge-ligand binding patterns using interaction fingerprints, thereby delineating 15 different hydrogen-bond interaction modes. We believe these results will be valuable for de novo drug design and/or scaffold hopping of kinase-targeted drugs.
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