ProfKin: A comprehensive web server for structure-based kinase profiling
ProfKin: A comprehensive web server for structure-based kinase profiling
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DOI：
10.1016/j.ejmech.2021.113772
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发表时间：
2021-08-17
影响因子：
6.7
通讯作者：
Li, Honglin
中科院分区：
文献类型：
--
作者：
Shen, Zihao;Yan, Yu-Hang;Li, Honglin
蛋白激酶是信号转导级联反应的中心介质，也是治疗干预的有吸引力的药物靶点。由于激酶在结构和机制上相互关联，激酶抑制剂的选择性通常通过激酶谱来研究，并被认为是药物发现的重要指标。我们在这里描述了一个多功能的Web服务器称为ProfKin的基于结构的激酶分析，这是基于激酶配体集中的数据库（KinLigDB）。它提供了涵盖297种人类激酶的4219种激酶-配体复合物结构的全部即用型三维结构坐标及相关信息，特别包括结合位点类型、结合配体类型、相互作用指纹、下游分子及相关人类疾病等。Web服务器通过预测查询分子的可能结合模式，通过相互作用指纹分析方法指导结合模式的优先级排序，并通过综合索引给出排序的激酶列表。用户可以自由选择整个或部分KinLigDB数据库，例如通过子家族和结合位点类型，以自定义分析内容。查询分子的预测结合位姿与参考结合模式的叠加可以在网站上目视检查。还为每个排名靠前的激酶提供了额外的分类属性和系统发育树。(C)2021 Elsevier Masson SAS。All rights reserved.
Protein kinases are central mediators of signal-transduction cascades and attractive drug targets for therapeutic intervention. Since kinases are structurally and mechanistically related to each other, kinase inhibitor selectivity is often investigated by kinase profiling and considered as an important index for drug discovery. We here describe a versatile web server termed ProfKin for structure-based kinase profiling, which is based on a kinase-ligand focused database (KinLigDB). It provides all ready-to-use 3D structure coordinates of 4219 kinase-ligand complex structures covering 297 human kinases and the associated information, particularly including binding site type, binding ligand type, interaction fingerprints, downstream molecules and related human diseases. The web server works via predicting possible binding modes for the query molecule, prioritizing the binding modes guided by an interaction fingerprint analysis method, and giving a list of ranked kinases by a comprehensive index. Users can freely select entire or part of the KinLigDB database, e.g. via subfamily and binding site type, to customize the profiling contents. The superimpositions of the predicted binding poses of the query molecule with reference binding modes can be visually inspected on the website. The additional classification attributes and phylogenetic tree are also given for each top-ranked kinase. (C) 2021 Elsevier Masson SAS. All rights reserved.