The WAC™ method is based on covalent immobilisation of a protein to be screened on a standard high-performance liquid chromatograph (HPLC) column. The solution of small molecular weight fragments is subsequently injected into the column. During elution, the fragments that have higher affinity for the protein will stay on the column longer than those with low or no affinity. The fragments can be conveniently detected using mass or UV spectrometry. This method is an efficient and lower-cost choice, compared to other methods that study ligand binding, e.g., X-ray crystallography, NMR spectroscopy or isothermal titration calorimetry (ITC). After the initial hit identification, NMR spectroscopy and X-ray crystallography may be used to gain additional insights into the details of the interactions of the fragments with the protein binding site, the amino acid resides involved in the interactions, types of interactions, etc. Ligand efficiency and ligand binding energy may subsequently be calculated.