发现具有柔性受体对接方案的新型 Pim-1 激酶抑制剂。
Discovery of Novel Pim-1 Kinase Inhibitors with a Flexible-Receptor Docking Protocol.
机构信息
State Key Laboratory of Chemical Resources Engineering , Beijing University of Chemical Technology , Beijing 100029 , China.
National Institute of Biological Sciences , No. 7 Science Park Road, Zhongguancun Life Science Park , Beijing 102206 , China.
出版信息
J Chem Inf Model. 2019 Oct 28;59(10):4116-4119. doi: 10.1021/acs.jcim.9b00494. Epub 2019 Oct 17.
A flexible-receptor docking protocol was designed for treating binding-site side-chain flexibility by integrating essential aspects of "Conformational Selection" and "Induced Fit" in a hierarchical fashion. Assessed in a diverse set of pharmaceutically relevant targets, this protocol showed improved performance in reproducing binding poses and ligand enrichment studies compared to rigid-receptor docking. Moreover, it has also exhibited encouraging efficiency in prospective ligand discovery for Pim-1 kinase, which led to novel Pim-1 inhibitors with single-digit nanomolar potencies.
设计了一种灵活受体对接方案，通过分层集成“构象选择”和“诱导契合”的基本方面来处理结合位侧链柔性。在一系列多样化的药物相关靶标中进行评估，与刚性受体对接相比，该方案在重现结合构象和配体富集研究方面表现出了更好的性能。此外，它在 Pim-1 激酶的前瞻性配体发现方面也表现出了令人鼓舞的效率，从而发现了具有个位数纳摩尔效力的新型 Pim-1 抑制剂。
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