Improved Method for the Identification and Validation of Allosteric Sites
Improved Method for the Identification and Validation of Allosteric Sites
复制标题
改进的变构位点识别和验证方法。
DOI：
10.1021/acs.jcim.7b00014
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发表时间：
2017-09-01
影响因子：
5.6
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Song, Kun;Liu, Xinyi;Zhang, Jian
Allosteric regulation induced by modulators binding to different, often distant, allosteric sites allows for exquisite control of protein functional activity. The structural diversity of allosteric sites endows allosteric modulators with high selectivity and low toxicity. Targeting allosteric sites, a novel tactic in drug discovery, has garnered much attention in the scientific community, and the identification of allosteric sites has become an important component of the development of allosteric drugs. Here we present AllositePro, a method which predicts allosteric sites in proteins by combining pocket features with perturbation analysis. The performance of AllositePro is superior to that of the other currently available methods. Using AllositePro, we predicted a novel allosteric site in cyclin-dependent kinase 2 (CDK2,) and validated it by site-directed mutagenesis assay. Thus, the AllositePro method provides an effective way to identify allosteric sites and could be a useful strategy for allosteric drug discovery.
