Zhao Zheng, Bourne Philip E
School of Data Science and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
ACS Med Chem Lett. 2023 Oct 9;14(11):1503-1508. doi: 10.1021/acsmedchemlett.3c00212. eCollection 2023 Nov 9.
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 drug design and/or scaffold hopping of kinase-targeted drugs.
ATP竞争性激酶抑制剂在腺嘌呤结合位点与激酶铰链区形成氢键相互作用。因此，作为合理药物设计策略的一部分，探索铰链-配体识别至关重要。在此，利用已知的配体结合激酶结构和实验检测资源，我们首先创建了一个包含2705个纳摩尔级配体结合激酶复合物的激酶结构-检测数据库（KSAD）。然后，使用KSAD，我们通过相互作用指纹系统地研究铰链-配体结合模式，从而描绘出15种不同的氢键相互作用模式。我们相信这些结果将对激酶靶向药物的药物设计和/或骨架跃迁有价值。
