Accurately characterising fragment-protein interactions is therefore central to the FBDD process. Despite substantial improvements in leveraging in vitro methods for fragment screening , this remains a challenging task. By their nature fragments tend to be low affinity binders, somewhere in the millimolar to micromolar range, with a propensity to access multiple binding sites in a protein target. Not only do highly sensitive affinity measurements need to be employed, something that cannot always be readily used for large fragment screens, but multiple orthogonal methods are often required to validate low affinity hits .