Structural dynamics in biomolecular interactions
The mechanisms of cellular processes are dictated by biomolecular interactions. Regulation of such mechanisms is typically achieved on the level of dynamics in biomolecules, particularly through kinetic modulation of their structure. Biomolecules are not static objects but adopt dynamically different thermodynamic states. We characterize fundamental principles of biomolecular dynamics at atomic resolution by analyzing molecular interactions involving proteins, nucleic acids, lipids, small molecules, and carbohydrates. We study selected examples of such interactions, which play essential roles in a diverse array of biological processes, e.g., epitranscriptomics, non-canonical eukaryotic translation initiation, oncogenesis, and antibiotic mechanisms. To gain atomic-detail insight into the underlying molecular mechanisms, we employ Nuclear Magnetic Resonance (NMR) spectroscopy focusing on dynamic aspects of the interactions. Our studies aim to help further establish the relevance of changes from unstructured to structured molecular architectures of proteins in the context of biomolecular interactions.
NMR is a powerful tool to study changes in conformation and chemical features of biomolecules
We focus specifically on characterizing two aspects of biomolecular dynamics by NMR. Firstly, we analyze conformational changes in biomolecules upon interaction, e.g., movements of domains or subunits of proteins and nucleic acids, of amino acid side chains or bases in nucleotides (such as rotations), and local movements, for example of protein loops. In the context of intrinsically disordered proteins (IDPs), we also study disorder-to-order transitions. Secondly, we investigate the effect of changes in chemical features of functional groups on structure and dynamics of biomolecules. This concerns localization and distribution of charge, protonation state, changes in hydrogen bonding networks, and modification of nucleotide bases (e.g., N6-methylation of adenosine, m6A) in nucleic acids or amino acids (e.g., serine phosphorylation) in proteins.
Collaborations
We are a highly collaborative group and are always looking for new research cooperation. Please contact Daniel Friedrich (daniel.friedrich[at]uni-koeln.de) if you want to work with us on understanding biomolecular function by NMR.
We are currently working with the groups of Bart Thomma (Department of Biology, University of Cologne) and Alvaro Mallagaray (Institute of Chemistry and Metabolomics, University of Lübeck) on protein-cell wall interactions, with the lab of Ines Neundorf (Department of Chemistry and Biochemistry, University of Cologne) on structural characterization of antimicrobial peptides and with the group of Uli Baumann (Department of Chemistry and Biochemistry, University of Cologne) on analyzing protein-protein interactions. We are also associated with the Collaborative Research Center (CRC) 1211 of the Deutsche Forschungsgemeinschaft.