Profile

Organisation
The NMR group is part of the Molecular Dynamics research group, embedded in the Groningen Biomolecular Sciences and Biotechnology Institute (GBB) at the University of Groningen. We are a part of the Faculty of Mathematics and Natural Sciences.

 

Current research topics

The NMR group focuses primarily on the relationship between protein structure, function and dynamics. In addition, we design novel NMR experiments.
We collaborate with many groups, ranging from theoretical chemists and mathematicians to medical doctors and cover a wide spectrum of activities. These include, but are not limited to, studies of protein electrostatics, calculations of experimental NMR parameters such as nuclear shielding tensors, protein structure determination, enzyme functional dynamics, peptide aggregation and bacterial metabolism.

 

Major results

A keystone of structural molecular biology is the assertion that a specific function of a protein is determined by its unique and rigid three-dimensional (3D) structure. This idea, formulated more than 100 years ago as a lock-and-key model for explaining the amazing specificity of enzymatic hydrolysis, proved to be extremely fruitful. Although it has been realized that flexibility is key to their function, enzymes are still archetypical examples of the exact positioning of amino acid side chains for function through a well-defined structural framework. However, a re-examination of the protein structure–function relationship is now warranted based on systematic studies of intrinsically unfolded/disordered proteins. There are two major reasons for this reappraisal: (1) the results of bioinformatics analyses of the genomic codes for protein amino acid sequences, and (2) the accumulation of experimental evidence for the existence of a rather large number of protein domains and even entire proteins, lacking ordered structure under physiological conditions. The NMR group currently studies the inherently dynamic structures of several natively disordered human proteins. Some of these naturally occurring proteins tend to spontaneously self-associate as oligomers, and ultimately are deposited into insoluble fibers. We are particularly interested in the relationship between the early steps of transient structure formation and their relationship to fibril formation and growth. This work is of great importance, as protein aggregation behaviour is intimately connected to human pathology. Proteins that are currently being studied in our lab include alpha-synuclein (Parkinson's disease), amyloid-beta and tau (Alzheimer's disease) and neuroligin (autism spectrum disorder). As disordered proteins are challenging to work with, a large part of our work involved the continuous development of new experiments to study ever larger and more complex systems.