The ability to obtain information about the structure and dynamics of proteins with atomic resolution allows, for example, the optimization of biomolecules in industrially and socially relevant areas as the basis for a future-oriented and functioning bioeconomy.
The problems and scientific topics in the interdisciplinary field of structural biology are largely defined by the methods to be used:
X-ray structure analysis: protein crystallography is the most widely used technique for obtaining static, high-resolution structures of large macromolecules. This detailed structural information allows, for example, the elucidation of catalytic mechanisms or identification of substrate and inhibitor binding sites. Currently, the main challenge is to determine the structure of supra-molecular complexes and molecular machines. In addition, the prediction of conformational changes, the determination of affinity and specificity of protein-protein interactions and the determination of structure of reaction intermediates remain important tasks.
Biomolecular NMR spectroscopy: determination of the structure of small and medium-sized proteins has been a standard task of liquid NMR spectroscopy for many years. In addition, characterization of the dynamics of this biomolecule at different time scales has been perfected over the past few years. This is certainly one of the greatest strengths of NMR. The characterization of protein-ligand interactions is also possible using a variety of experiments. Current challenges lie in the shifting the molecular weight limits of the macromolecules to be examined upwards and the structural characterization of membrane proteins, fibril-forming proteins and intrinsically unstructured proteins. Even the determination of the structure of low populated conformations has come within the reach of this technology within the last years. In recent years, solid-state NMR spectroscopy has been developed so far that it is in principle possible to investigate the structure and dynamics of proteins that can neither be crystallized nor solubilized and hence are not accessible through the two methods mentioned above.