- Structural biology of protein-DNA complexes
- Small molecule inhibitors
- NMR structure determination of large proteins
- Biochemical and structural characterization of protein-DNA interactions involved in DNA repair and transcription
- Design and pre-clinical evaluation of compounds for lead optimization
- Development of integrated structural approaches for studying large biomolecules in solution
Content of research
We use NMR and hybrid structural methods, as well as biophysical techniques, to study protein-DNA complexes involved in DNA repair and transcription. Both topics involve proteins that are promising targets for anti-cancer drugs. Therefore the group has a strong interest in structure-based drug design.
Protein-DNA transactions are essential for genome maintenance. We use structural, biochemical, and computational tools to study the function of DNA-repair factors. We employ a combination of solution techniques (NMR, SAXS-SANS, FRET) to structurally characterize protein-DNA complexes and understand dynamic rearrangements induced upon DNA binding. Structural findings are complemented in a broader functional context by genetic, molecular or cell biology, and single-molecule assays (L. Krejci, Masaryk University).
DNA repair as a therapeutic target has received considerable attention owing to the promise of drugs that target DNA-repair enzymes and potentiate conventional cytotoxic therapy through mechanism-based approaches. In this direction, we study the binding of small molecules to protein targets of interest, in order to modulate their function for potential therapeutic benefit. Promising inhibitors are identified based on in silico design (Prof. E. Mikros, University of Athens; Prof. J. Tuszynski, University of Alberta) or high-throughput screening (P. Bartunek, IMG Prague).