SAR by NMR spectroscopy allows researchers to observe directly ligand binding [247] in both solution state and solid-state spectra [253], increasing the method’s versatility [254]. It works particularly well for targeting proteins with adjacent “subpocket” binding sites [248]. Furthermore, SAR by NMR is cost-effective when combined with HTS (High Throughput Screening) [255]. SAR by NMR can also be used even when atomic peak assignments in spectra are unknown, though it is much more powerful when the resonance frequency of each atom is known [254]. The main limitation of SAR by NMR, however, is its inability to distinguish between multiple binding modes (i.e., cleavage of covalent bonds or allosteric changes), and if multiple binding modes are present, it can be difficult to pinpoint the “true” binding site of the ligand solely using data obtained using SAR by NMR [254].