Discovery of Novel Pim-1 Kinase Inhibitors with a Flexible-Receptor Docking Protocol
Gudong Li1, Wei Li2, Yuting Xie2
1State Key Laboratory of Chemical Resources Engineering , Beijing University of Chemical Technology , Beijing 100029 , China.
Abstract:
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.
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