The research in the NMR Spectroscopy group is others focused on the elucidation of the molecular structure of protein-protein and protein-nucleic acid complexes or membrane proteins, using NMR spectroscopic techniques, which are in many cases specifically developed in the group for answering specific questions on the nature and extent of the interacting groups and atoms. NMR spectra provide information on the geometry of direct neighbour groups in a molecule and on the spatial proximity of hydrogen atoms in the molecule. To obtain the necessary data, several kinds of mostly multi-dimensional NMR experiments have to be performed. These data can be transformed into realistic three dimensional molecular structures by extensive computer calculations, with methods adopted from computational chemistry techniques.
Many chemical and biological processes take place in a non-crystalline environment or concern molecules with reduced molecular mobility. Important examples include polymers, protein aggregates or membrane proteins. These systems are intimately related to questions such as: – How is information transmitted across the cellular membrane? – Which factors impede correct protein folding? – How does a fuel cell work? Magnetic Resonance in the solid-state (solid-state NMR) is a tool to answer such questions on the molecular level. Progress in solid-state NMR methodology, instrumentation and sample preparation permit us to study molecular structure and dynamics with increasing accuracy and flexibility. Solid-state NMR is increasingly used in physical chemistry, biophysics and structural biology. Our studies often involve the combined application of solid-state NMR and other biophysical methods and can find direct application in research areas such as nanotechnology or pharmacology.
Research within the computational structural biology group of prof. dr. Alexandre Bonvin focuses on the development of reliable bioinformatics and computational approaches to predict, model and dissect biomolecular interactions at atomic level. For this, bioinformatics data, structural information and available biochemical or biophysical experimental data are combined to drive the modelling process. This is implemented and further developed in the widely used HADDOCK software for the modelling of biomolecular complexes. By following a holistic approach integrating various experimental information sources with computational structural biology methods we aim at obtaining a comprehensive description of the structural and dynamic landscape of complex biomolecular machines, adding the structural dimension to interaction networks and opening the route to systematic and genome-wide studies of biomolecular interactions.
The research of prof. dr. Rolf Boelens is focused on the elucidation of the molecular basis of protein-DNA recognition, using NMR spectroscopic techniques, which are in many cases specifically developed in the Department for answering specific questions on the nature and extent of the interacting groups and atoms. NMR spectra provide information on the geometry of direct neighbour groups in a molecule and on the spatial proximity of hydrogen atoms in the molecule. To obtain the necessary data, several kinds of mostly multi-dimensional NMR experiments have to be performed. These data can be transformed into realistic three dimensional molecular structures by extensive computer calculations, with methods adopted from computational chemistry techniques.
Prof. dr. Marc Baldus is a world leading expert in solid state NMR spectroscopy (ssNMR). His research focuses on development and application of high resolution ssNMR to study 3D molecular structure and dynamics in complex biological molecules in relationship to their function. He has studied potassium ion channels in the context of a membrane, on the atomic level and determined the structural changes following inactivation of the channel in a membrane environment as well as the coupling of activation and inactivation gates. More recently, he has been pioneering novel methods to study biomolecular structures in a native cellular enviroment at atomic resolution, a technology that classically suffers from low sensitivity. He was the first in the world to show that by using dynamic nuclear polarization, it is possible to enhance the sensitivity of ssNMR such that it is possible to obtain high-resolution ssNMR spectra, and thus structural information, from complex molecular structures, including integral membrane proteins, in their native cellular environment.
Dr. Gert Folkers is assistant professor and has implemented the HTP cloning and expression systems of the NMR spectroscopy group for the screening of multiple constructs and culture conditions enabling optimization of growth and induction conditions. The availability of an effective protein production facility allowed the group to participate in European structural genomics initiatives and led over the years to the submission of over 20 structures to the PDB.
Research within the group of dr. Markus Weingarth focuses on the development of modern sensitivity-enhanced solid-state NMR methods and their integration with computational techniques. We use our methods to study pharmaceutically important systems such as nanoscale drug-vectors and membrane-embedded drug-receptor complexes. We strive to study these complex biological assemblies at truly physiological conditions and at the atomic level.
Dr. Klaartje Houben is scientific supervisor of the uNMR-NL (ultra-high field NMR facility for The Netherlands) consortium and manager of the Utrecht NMR facility. The NMR facility provides access to high-field NMR spectrometers for scientists from research institutes as well as companies in the field of Life and Material sciences. Klaartje’s research focuses on the structure and dynamics of membrane proteins in a native(-like) environment. In order to get high resolution and atomic detailed information, she applies a divide-and-conquer approach by combining both liquid-state NMR data on soluble protein constructs with solid-state NMR data on full membrane protein preparations.
Dr. Hans Wienk is the project manager of the EU-funded structural biology initiative iNEXT, where he monitors the progress of the project, prepares reports, organizes periodical meetings, and delivers guidelines, procedures and communication material to the consortium. He is also facility manager at the Utrecht NMR facility, where he supervises the performance of the solution state NMR spectrometers in the group, ranging from 500-950 MHz. Most of the research he is involved in relates to the application of solution state NMR techniques to diverse, mainly biologically relevant systems. Focus lies on the determination of structure, function and dynamics of proteins.