Structural NMR

Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a technique which exploits the magnetic properties of nuclei with nonzero spin. It is a versatile method that can be used to derive chemical and structural information from molecules, both small (e.g., drugs) and large (proteins).

Relevance of NMR

Crystallography is the method of choice for high resolution structures but the difficulty of obtaining crystals as well as problems caused by more complicated systems such as protein complexes and mixtures often hamper the use of this method. NMR is a very well known alternative, which can complement crystallography. It is also useful for protein quality control and as a tool for fast identification of proteins suitable for crystallization.

Due to limitations of current methods and instruments, the largest size of proteins from which full structural information can be obtained is about 20 kDa. Apart from structural studies, NMR spectroscopy be used for drug screening and hit optimization, mapping of protein-ligand interactions during drug discovery process, Structure-Activity relationships by NMR and also to study protein-protein complexes.

Advantages of NMR

The main advantage of NMR is that it mostly works in solution, with experimental conditions much closer to real life.

× Structural information of proteins that do not crystallize.

× Drug screening techniques enable NMR to evaluate the efficiency of lead compounds and provide feedback that can lead to improvements in their functions (Structure-Activity relationships by NMR)

¹⁵N HSQC NMR spectrum of a 20 kDa protein "Sausage" C^a diagram of the protein structure derived from the NMR data

Disadvantages of NMR

× great complexity

× high cost of instrumentation

× highly specialized experts needed for the data interpretation

Equipment Resources

Bruker Avance III 800     Bruker Avance II/III 500      Bruker Avance 400