Veenbaas Seth D, Felder Simon, Weeks Kevin M
Department of Chemistry, University of North Carolina, Chapel Hill NC 27599-3290.
bioRxiv. 2025 Mar 29:2025.03.25.645323. doi: 10.1101/2025.03.25.645323.
Small molecules that bind specific sites in RNAs hold promise for altering RNA function, manipulating gene expression, and expanding the scope of druggable targets beyond proteins. Identifying binding sites in RNA that can engage ligands with good physicochemical properties remains a significant challenge. is a software package for identifying, characterizing, and visualizing ligand-binding sites in RNA was optimized, through comprehensive analysis of currently available RNA-ligand complexes, to identify pockets in RNAs able to bind small molecules possessing favorable properties, generally termed drug-like. Here, we demonstrate use of to analyze RNA-ligand interactions and novel pockets in small and large RNAs, to assess ensembles of RNA structure models, and to identify pockets in dynamic RNA systems. performs best with RNA structures visualized at high (≤3.5 Å) resolution, but also provides useful information with lower resolution structures and computational models. is a powerful, freely available tool for discovery and analysis of ligand-binding pockets in RNA molecules.
能够结合RNA特定位点的小分子有望改变RNA功能、调控基因表达,并拓展除蛋白质之外的可成药靶点范围。识别能与具有良好物理化学性质的配体结合的RNA结合位点仍然是一项重大挑战。 是一个用于识别、表征和可视化RNA中配体结合位点的软件包,通过对当前可用的RNA-配体复合物进行全面分析进行了优化,以识别RNA中能够结合具有良好性质(通常称为类药物性质)的小分子的口袋。在这里,我们展示了使用 来分析RNA-配体相互作用以及大小RNA中的新口袋,评估RNA结构模型的集合,并识别动态RNA系统中的口袋。 在高分辨率(≤3.5 Å)下可视化的RNA结构上表现最佳,但对于较低分辨率的结构和计算模型也能提供有用信息。 是用于发现和分析RNA分子中配体结合口袋的强大且免费的工具。