Research

Our group is interested in the determination of structure and dynamics of a variety of molecules of chemical and biological interest, organic synthesis of biologically relevant compounds and nmr method development.

Our research topics

Development of New NMR Techniques for Monitoring of Protein Folding with Atomic Resolution

We have developed two independent methods to study structural transitions and reactions by time-resolved NMR spectroscopy with millisecond dead-time. Therefore, on one hand, we use a rapid mixing system inside the active volume in the probe, which we developed in cooperation with BRUKER. In addition, we have developed a method to laser-trigger cofactor dependent reactions inside the NMR tube which we established.

Protein folding and misfolding

Regarding protein folding, we are able to analyse the starting point of folding, the unfolded state of proteins, by NMR spectroscopy (Klein-Seetharaman et al., Science 2002) as well as kinetics of folding and misfolding (Schlepckow et al., Angew. Chem. 2013) and the structure of the folded state.

RNA-based regulation

As recently discovered, RNA plays a central role in cellular regulation of transcription (Steinert et al., eLife 2017) and translation (Reining et al., Nature 2013). We investigate how riboswitch RNAs sense changes in metabolite concentration and how they kinetically influence gene expression.

Structure-based drug design

By integrated structural biology (NMR, X-ray) and biophysics (MST, ITC CD), chemical synthesis and cell biology, we contribute to the development of new drug candidates, especially in the field of cancer (C. Herbert et al.,Cancer Cell 2013; Vogtherr et al., Angew. Chem. 2005).

Membrane Proteins

We investigate light-absorbing complexes such as rhodopsin in order to understand how our eyes sense light. In particular, we apply time-resolved NMR spectroscopy to investigate branched photo-cycles (Chatterjee et al., Angew Chem. 2014). We also contribute to structural characterization of the respiratory chain complexes by synthesis of specific inhibitors (Zickermann et al., Science 2015).

Paramagnetic‑iterative relaxation matrix approach: extracting PRE‑restraints from NOESY spectra for 3D structure elucidation of biomolecules

Supporting Information for the publication "Paramagnetic-Iterative Relaxation Matrix Approach – Extracting PRE-Restraints from NOESY Spectra for 3D Structure Elucidation of Biomolecules" published in Journal of Biomolecular NMR. Files and scipts can be found at: https://osf.io/6adrz/

G-quadruplexes

G-quadruplexes are important drug targets in anticancer research. In our group, we apply NMR spectroscopy to investigate structural polymorphism of G-quadruplexes as well as real-time NMR to gain insight into folding pathways (Bessi et al., Angew Chem 2015). Further, we solve NMR structures of the holo and apo states of physiologically relevant G quadruplex drug targets (Wirmer-Bartoschek et al., Angew Chem 2017), and we apply state-of-the-art NMR methods to investigate G4-ligand interactions (Bessi et al., ACS Chem Biol. 2012).
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Prof. Dr. Harald Schwalbe
Institut für Organische Chemie und Chemische Biologie
Johann Wolfgang Goethe Universität
Max-von-Laue-Str. 7
D-60438 Frankfurt am Main
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