The generation of new drug candidates requires the identification and optimisation of compounds that bind specifically to drug targets. This process is usually conducted in a multi-step linear manner. Our research aims to short-circuit the generation of such compounds by developing novel screening methods that simultaneously report the compound binding event, site and orientation on the target. We capitalise on state-of-the-art biophysical methods (e.g. paramagnetic NMR spectroscopy) and screening platforms (e.g. fragment-based drug discovery).