NMR-Based Structural Biology

While crystallography is a powerful method to obtain high resolution structure information, it is not always successful. ZoBio has extensive experience in the elucidation of the 3D structure of target-ligand complexes using NMR. Starting with simple but efficient ligand based methods when protein observed methods are not applicable. If a protein can be isotope labelled and is of a moderate size (< 40 kDa) then the full range of NMR tools are available including binding site mapping, resonance assignment and structure elucidation via NOE. For many proteins a structure may already be available.

In such cases an alternative approach is available that is both efficient and accurate. Here, only the CH3 groups of I, L & V residues (depicted as balls) are isotope labelled. The red and blue methyl groups are sufficiently close (~8 Å) to 1H’s of the ligand to give rise to NOEs (schematically shown on the left). The intermolecular NOEs can be used to calculate the structure of the complex even when the target is 100 kDa or more.