R-BIND: An Interactive Database for Exploring and Developing RNA Targeted Chemical Probes
R-BIND: An Interactive Database for Exploring and Developing RNA Targeted Chemical Probes
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DOI：
10.1021/acschembio.9b00631
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发表时间：
2019-12-01
影响因子：
4
通讯作者：
Hargrove, Amanda E.
中科院分区：
文献类型：
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作者：
Morgan, Brittany S.;Sanaba, Bilva G.;Hargrove, Amanda E.
虽然用小分子靶向 RNA 的机会已得到广泛认可，但在生物系统中实现特异性 RNA 识别所面临的挑战阻碍了进展，并阻止了 RNA 靶向化学探针的发现以及许多研究人员进入该领域。为了方便后续应用，我们策划了RNA靶向生物活性配体数据库（R-BIND）。该集合包含一系列关于已报道的针对非 rRNA 并具有生物活性的化学探针的信息，分析已导致 RNA 特有特性的发现。在此，我们开发了一个在线平台，向社区免费提供这些信息，提供搜索选项、一套用于探针开发的工具以及更新的 R-BIND 数据集，其中包含每个探针的详细实验信息。我们对更新的 R-BIND 列表重复了之前的化学信息学分析，发现尽管数据库大小增加了近 50%，但显着的物理化学、结构和空间特性保持不变。此外，我们开发了几种用户友好的工具，包括基于化学信息学参数、实验细节、功能组和子结构的查询。此外，最近邻算法可以评估用户上传的分子与 R-BIND 配体的相似性。这些工具和资源可用于设计小分子库、优化先导配体或选择靶标、探针、测定和对照实验。化学探针对于研究和发现 RNA 新功能至关重要，我们希望该资源能够极大地帮助研究人员探索和开发成功的 RNA 靶向探针。
While the opportunities available for targeting RNA with small molecules have been widely appreciated, the challenges associated with achieving specific RNA recognition in biological systems have hindered progress and prevented discovery of RNA-targeted chemical probes and theirmany researchers from entering the field. To facilitate the subsequent applications, we curated the RNA-targeted BIoactive ligaNd Database (R-BIND). This collection contains an array of information on reported chemical probes that target non-rRNA and have biological activity, and analysis has led to the discovery of RNA-privileged properties. Herein, we developed an online platform to make this information freely available to the community, offering search options, a suite of tools for probe development, and an updated R-BIND data set with detailed experimental information for each probe. We repeated the previous cheminformatics analysis on the updated R-BIND list and found that the distinguishing physicochemical, structural, and spatial properties remained unchanged, despite an almost 50% increase in the database size. Further, we developed several user-friendly tools, including queries based on cheminformatic parameters, experimental details, functional groups, and substructures. In addition, a nearest neighbor algorithm can assess the similarity of user-uploaded molecules to R-BIND ligands. These tools and resources can be used to design small molecule libraries, optimize lead ligands, or select targets, probes, assays, and control experiments. Chemical probes are critical to the study and discovery of novel functions for RNA, and we expect this resource to greatly assist researchers in exploring and developing successful RNA-targeted probes.