Our leading NMR fragment and larger ligand screening services are often run within our integrated drug discovery services projects. We regularly run compound validation, either in combination with our proprietary weak-affinity chromatography (WAC™) or other biophysical screening methods. Depending on the target protein, we can run either 1D ligand-detection experiments or use 2D spectra. For 1D ligand detection, we can conduct either 1H or 19F experiments. We can identify potential binding sites by competition experiments with a known binder. In 2D experiments, the protein must generally be labeled with 15N (or 2H for large proteins). However, recent advances in NMR technology enable us to conduct NMR fragment screening on non-isotopically labeled samples by examining the methyl region of the 13C NMR spectrum. If the assignment is available, we can readily identify the binding epitope of various fragments at atomic resolution.
