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Intrinsically disordered proteins are highly dynamic biomolecules that rapidly interconvert between many structural conformations. Traditionally, these proteins have been considered un-druggable because of their lack of classical long-lived binding pockets. Recent evidence suggests that intrinsically disordered proteins can bind small, drug-like molecules, however, there are limited approaches to characterize these interactions experimentally. Here we demonstrate that ligand-detected 19 F transverse relaxation rates ( R 2 ) obtained from Nuclear Magnetic Resonance spectroscopy are highly sensitive to the interaction between a small-molecule and an intrinsically disordered protein, in contrast to chemical shift perturbations which are minimally sensitive for this interaction. With this method, we show that the small molecule, 5-fluoroindole, interacts with the disordered domains of non-structural protein 5A from hepatitis C virus with a K d of 260 ± 110 μM. We also demonstrate that 5-fluoroindole remains highly dynamic in the bound form. Our findings suggest that ligand-detected 19 F transverse relaxation measurements could represent a highly effective screening strategy to identify molecules capable of interacting with these traditionally elusive, dynamic biomolecules.