The fluorine ( 19 F) nucleus has several properties that makes it exceptionally powerful for biological NMR, and these have been exploited for decades. However, in recent years, there has been a strong resurgence in 19 F NMR spectroscopy, particularly for the study of large and complex biological systems that remain challenging for conventional approaches. This renewed interest has been enabled by advances in fluorine‐labelling strategies together with a growing toolkit of NMR experiments. In this review, we first outline new labelling strategies that permit the site‐specific incorporation of fluorine at strategic positions in proteins, including probes with very high signal intensity, enhanced sensitivity to the chemical environment, and tags that exploit the high‐resolution 19 F– 13 C TROSY effect. We then cover the expanding set of 19 F NMR experiments that use these probes to investigate both structure and dynamics across a wide range of timescales. Throughout the review, we highlight recent studies that exemplify these approaches, including work that integrates 19 F NMR measurements with complementary techniques to provide deeper insight into biomolecular mechanisms.
Burridge et al. (Sun,) studied this question.