R-BIND 2.0: An Updated Database of Bioactive RNA-Targeting Small Molecules and Associated RNA Secondary Structures.
R-BIND 2.0: An Updated Database of Bioactive RNA-Targeting Small Molecules and Associated RNA Secondary Structures.
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R-BIND 2.0：生物活性RNA靶向小分子和相关RNA二级结构的更新数据库。
DOI：
10.1021/acschembio.2c00224
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发表时间：
2022-06-17
影响因子：
4
通讯作者：
Hargrove, Amanda E.
中科院分区：
文献类型：
--
作者：
Donlic, Anita;Swanson, Emily G.;Chiu, Liang-Yuan;Wicks, Sarah L.;Juru, Aline Umuhire;Cai, Zhengguo;Kassam, Kamillah;Laudeman, Chris;Sanaba, Bilva G.;Sugarman, Andrew;Han, Eunseong;Tolbert, Blanton S.;Hargrove, Amanda E.
RNA在细胞生理学和病理学中的作用的发现增加了对调节这些生物分子结构和功能的新工具的需求，小分子被证明是有用的。2017年，我们策划了rna靶向生物活性配体数据库（R-BIND），并发现了rna靶向配体的独特物理化学性质，从而提出了“rna特权”化学空间的存在。两年一次的数据库更新和网站平台的建立（rbind.chem.duke.edu）为基于分析的物理化学和空间性质设计小分子提供了新的见解和工具。在这篇报告和R-BIND 2.0的更新中，我们改进了管理方法和配体分类系统，并首次对RNA结构元件进行了分析，以确定新的靶向策略。具体来说，我们策划和分析了RNA靶结构基序，以确定可能赋予不同RNA二级和三级结构选择性的小分子特性。此外，我们收集了目标结构序列，并将RNA结构搜索算法整合到网站中，该算法可以在没有先验二级结构知识的情况下输出针对相似基序的小分子。化学信息学分析显示，尽管小分子文库的大小增加了50%，但R-BIND配体的区别性质仍然与蛋白质有显著不同，因此仍然与rna靶向探针的发现有关。我们期望这些新的见解和网站功能能够使RNA靶向配体的合理设计成为可能，并为各种对RNA靶向感兴趣的科学家提供资源和灵感。
Discoveries of RNA roles in cellular physiology and pathology are increasing the need for new tools that modulate the structure and function of these biomolecules, and small molecules are proving useful. In 2017, we curated the RNA-targeted BIoactive ligaNd Database (R-BIND) and discovered distinguishing physicochemical properties of RNA-targeting ligands, leading us to propose the existence of an “RNA-privileged” chemical space. Biennial updates of the database and the establishment of a website platform (rbind.chem.duke.edu) have provided new insights and tools to design small molecules based on the analyzed physicochemical and spatial properties. In this report and R-BIND 2.0 update, we refined the curation approach and ligand classification system as well as conducted analyses of RNA structure elements for the first time to identify new targeting strategies. Specifically, we curated and analyzed RNA target structural motifs to determine the properties of small molecules that may confer selectivity for distinct RNA secondary and tertiary structures. Additionally, we collected sequences of target structures and incorporated an RNA structure search algorithm into the website that outputs small molecules targeting similar motifs without a priori secondary structure knowledge. Cheminformatic analyses revealed that, despite the 50% increase in small molecule library size, the distinguishing properties of R-BIND ligands remained significantly different from that of proteins and are therefore still relevant to RNA-targeted probe discovery. Combined, we expect these novel insights and website features to enable the rational design of RNA-targeted ligands and to serve as a resource and inspiration for a variety of scientists interested in RNA targeting.
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DOI：
10.1038/s41580-019-0136-0
发表时间：
2019-08
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Ganser LR;Kelly ML;Herschlag D;Al-Hashimi HM
通讯作者：
Al-Hashimi HM
影响因子：
7.3
作者：
Hermann, Thomas
通讯作者：
Hermann, Thomas
影响因子：
4
作者：
Morgan, Brittany S.;Sanaba, Bilva G.;Hargrove, Amanda E.
通讯作者：
Hargrove, Amanda E.
影响因子：
14.8
作者：
Fedorova O;Jagdmann GE Jr;Adams RL;Yuan L;Van Zandt MC;Pyle AM
通讯作者：
Pyle AM
影响因子：
16.2
作者：
Bernat V;Disney MD
通讯作者：
Disney MD