Biomolecular NMR Spectroscopy
Protein functions depend on 3D structure. We use NMR spectroscopy to assess the structure and structural changes of proteins and their complexes with other molecules (proteins, DNA, drugs). Using NMR spectroscopy, we can do this in aqueous solution, i.e. under near-physiological conditions. In particular, we develop new methods for studying complexes of greater molecular weight and of biological and medical interest.
Check out the project descriptions on the right and our recent publications for more information about current projects!
Chemical shift changes due to pseudocontact shifts
in a protein with Y
3+(black), Dy
3+ (red) or Er
3+ (pink).
Pseudocontact shifts are easy to measure.
3D model of the dengue virus NS2B/NS3 protease in complex with an inhibitor. We determined the binding mode of the inhibitor from pseudocontact shifts, using lanthanide tags at sites A-C.
Drug discovery
The vast majority of drugs are compounds that bind very tightly to a target protein. Knowing how they bind (site, structure, orientation) is key to finding improved molecules in a rational approach. We characterize the 3D structures of target proteins and their complexes with ligands by NMR spectroscopy. Find out more here.
Cell-free protein synthesis and unnatural amino acids
Making proteins from cDNA can be done in a day using cell-free protein synthesis. The technique is particularly suited for making proteins with selectively stable-isotope labelled proteins for NMR analysis. In addition, it enables efficient site-specific and selective incorporation of different unnatural amino acids. The group is a world-leader in the technology. Find out more here.
Lanthanide tags
Lanthanide ions are strong paramagnets. Site-specific attachment of a paramagnetic lanthanide to a protein generates large chemical shift changes in NMR spectra, which encode long-range structural restraints. The method provides structural information on protein-protein, protein-DNA and protein-ligand complexes with record-breaking speed and accuracy. Find out more here.
