文章基本信息

标题：Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling
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作者：Tianyi Qiu ; Dingfeng Wu ; Jingxuan Qiu 等
期刊名称：Journal of Cheminformatics
印刷版ISSN：1758-2946
电子版ISSN：1758-2946
出版年度：2018
卷号：10
期号：1
页码：21
DOI：10.1186/s13321-018-0275-x
语种：English
出版社：BioMed Central
摘要：Nuclear receptors (NR) are a class of proteins that are responsible for sensing steroid and thyroid hormones and certain other molecules. In that case, NR have the ability to regulate the expression of specific genes and associated with various diseases, which make it essential drug targets. Approaches which can predict the inhibition ability of compounds for different NR target should be particularly helpful for drug development. In this study, proteochemometric modelling was introduced to analysis the bioactivity between chemical compounds and NR targets. Results illustrated the ability of our PCM model for high-throughput NR-inhibitor screening after evaluated on both internal (AUC > 0.870) and external (AUC > 0.746) validation set. Moreover, in-silico predicted bioactive compounds were clustered according to structure similarity and a series of representative molecular scaffolds can be derived for five major NR targets. Through scaffolds analysis, those essential bioactive scaffolds of different NR target can be detected and compared. Generally, the methods and molecular scaffolds proposed in this article can not only help the screening of potential therapeutic NR-inhibitors but also able to guide the future NR-related drug discovery.
关键词：Proteochemometric modelling ; Nuclear receptor ; Molecular scaffold ; Cheminformatics