Sanofi, R&D, Data & In Silico Sciences, 91385 Chilly Mazarin, France.
Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR 3528, 75015 Paris, France.
Bioinformatics. 2022 Sep 2;38(17):4185-4193. doi: 10.1093/bioinformatics/btac483.
RNA molecules are implicated in numerous fundamental biological processes and many human pathologies, such as cancer, neurodegenerative disorders, muscular diseases and bacterial infections. Modulating the mode of action of disease-implicated RNA molecules can lead to the discovery of new therapeutical agents and even address pathologies linked to 'undruggable' protein targets. This modulation can be achieved by direct targeting of RNA with small molecules. As of today, only a few RNA-targeting small molecules are used clinically. One of the main obstacles that have hampered the development of a rational drug design protocol to target RNA with small molecules is the lack of a comprehensive understanding of the molecular mechanisms at the basis of RNA-small molecule (RNA-SM) recognition.
Here, we present Harnessing RIBOnucleic acid-Small molecule Structures (HARIBOSS), a curated collection of RNA-SM structures determined by X-ray crystallography, nuclear magnetic resonance spectroscopy and cryo-electron microscopy. HARIBOSS facilitates the exploration of drug-like compounds known to bind RNA, the analysis of ligands and pockets properties and ultimately the development of in silico strategies to identify RNA-targeting small molecules.
HARIBOSS can be explored via a web interface available at http://hariboss.pasteur.cloud.
Supplementary data are available at Bioinformatics online.
RNA 分子参与了许多基本的生物过程和许多人类疾病，如癌症、神经退行性疾病、肌肉疾病和细菌感染。调节与疾病相关的 RNA 分子的作用模式可以导致新的治疗剂的发现，甚至可以解决与“不可成药”的蛋白质靶标相关的病理学。这种调节可以通过小分子直接靶向 RNA 来实现。截至今天，只有少数几种靶向 RNA 的小分子在临床上使用。阻碍小分子靶向 RNA 的合理药物设计方案发展的主要障碍之一是缺乏对 RNA-小分子 (RNA-SM) 识别基础的分子机制的全面理解。
在这里，我们提出了利用核糖核酸小分子结构（HARIBOSS），这是一个通过 X 射线晶体学、核磁共振波谱学和低温电子显微镜确定的 RNA-SM 结构的 curated 集合。HARIBOSS 有助于探索已知与 RNA 结合的类药化合物，分析配体和口袋性质，并最终开发识别 RNA 靶向小分子的计算策略。
HARIBOSS 可以通过 http://hariboss.pasteur.cloud 上的 web 界面进行探索。
补充数据可在生物信息学在线获得。
