ci9b00494_si_001.pdf (1.94 MB)
Discovery of Novel Pim‑1 Kinase Inhibitors with a Flexible-Receptor Docking Protocol
journal contribution
posted on 2019-10-17, 18:40 authored by Gudong Li, Wei Li, Yuting Xie, Xiaobo Wan, Guojun Zheng, Niu Huang, Yu ZhouA 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.