19F NMR in RNA structural biology: exploring structures, dynamics, and small molecule interactions

Abstract

RNA molecules play essential roles in numerous biological pathways, making them attractive targets for drug discovery. Despite the challenges in developing small molecules targeting RNA, the success in developing compounds that modulate RNA function underscores its therapeutic potential. ¹⁹F NMR spectroscopy has emerged as a powerful tool in structural biology and drug discovery, particularly for studying macromolecular structures and ligand interactions. As RNA continues to gain prominence as a drug target, ¹⁹F NMR is expected to play a pivotal role in advancing RNA-focused drug discovery. This review describes the diverse applications of ¹⁹F NMR in RNA biology, including its use in characterizing RNA structures, probing molecular dynamics, identifying small-molecule binders, and investigating interaction mechanisms of small-molecule ligands. By providing detailed structural and ligand binding insights, ¹⁹F NMR will facilitate the discovery of RNA-targeting therapeutics and deepen our understanding of RNA modulatory mechanisms.