Target based screening typically utilizes the “SAR by NMR” (structure-activity-relationship by nuclear magnetic resonance) approach [246]. SAR is primarily used to identify and develop extremely tight-binding ligands [247]. The ligand to target binding is traditionally monitored via chemical shift changes [247] using a correlation spectroscopy such as 1H-15N HSQC starting with the target and no ligand present [248]. Multiple spectra for the target are recorded in the presence and absence of ligands. The binding ligand will cause chemical shift perturbations in the target, and these perturbations are often easily visualized by overlaying the two spectra [247]. For example Hajduk et al. investigated the binding interactions of 2-phenylimidazole with the FKBP protein as shown in Figure 7 [249].