Discovery of Novel Pim-1 Kinase Inhibitors with a Flexible-Receptor Docking Protocol

被引：11
|
作者：
Li, Gudong [1 ]
Li, Wei [2 ]
Xie, Yuting [2 ]
Wan, Xiaobo [2 ]
Zheng, Guojun [1 ]
Huang, Niu [2 ,3 ]
Zhou, Yu [2 ]
机构：
[1] Beijing Univ Chem Technol, State Key Lab Chem Resources Engn, Beijing 100029, Peoples R China
[2] Natl Inst Biol Sci, 7 Sci Pk Rd,Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China
[3] Tsinghua Univ, Tsinghua Inst Multidisciplinary Biomed Res, Beijing 102206, Peoples R China
来源：
JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2019年 / 59卷 / 10期
基金：
中国国家自然科学基金;
关键词：
SIDE-CHAIN; PROTEIN; MODEL; FLEXIBILITY;
D O I：
10.1021/acs.jcim.9b00494
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
引用
收藏
页码：4116 / 4119
页数：4
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