Discovery of Novel Pim-1 Kinase Inhibitors with a Flexible-Receptor Docking Protocol
Discovery of Novel Pim-1 Kinase Inhibitors with a Flexible-Receptor Docking Protocol
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利用灵活受体对接方案发现新型 Pim-1 激酶抑制剂
DOI：
10.1021/acs.jcim.9b00494
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Zhou, Yu
中科院分区：
文献类型：
--
作者：
Li, Gudong;Li, Wei;Zhou, Yu
设计了一种柔性受体对接方案，通过分层方式整合“构象选择”和“诱导匹配”的基本方面来处理结合位点侧链的灵活性。在多种药学相关靶标中进行评估，与刚性受体对接相比，该方案在再现结合姿势和配体富集研究方面表现出更好的性能。此外，它还在Pim-1激酶的预期配体发现方面表现出令人鼓舞的效率，这导致了具有个位数纳米摩尔效力的新型Pim-1抑制剂。
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.