Our research interests focus on the function and dynamics of proteins, nucleic acids and membranes with the goal of inhibiting their cellular activities using small molecules, peptides or short oligonucleotide mimics.
For many years, we have focused on aminoglycoside antibiotics that target bacterial ribosomal RNA, the macromolecular complex responsible for protein synthesis in the cell. We have also studied other non-coding bacterial RNAs and their inhibition by anti-sense modified oligonucleotides. We have investigated the use of peptide nucleic acids as inhibitors of bacterial RNA and searched for carriers to deliver them to bacterial cells. Among these carriers are cell-penetrating peptides, vitamin B12 and siderophores.
Another area of our research focuses on proteases, especially viral ones. We investigate how macromolecular crowding affects their dynamics and enzymatic activities.
We combine theoretical approaches (computational simulations and molecular modeling) with experimental biophysical measurements (absorbance, fluorescence, circular dichroism spectroscopy, isothermal titration calorimetry) and microbiology.
In our research on targeting bacteria with aminoglycosides, membrane-active peptides and modified oligonucleotides, we address the following research questions:
- How can we improve aminoglycoside antibiotics?
- How can we design effective antibacterial peptides?
- How can we find suitable cellular targets for antibacterial peptide nucleic acids?
- How can we deliver peptide nucleic acid oligomers to bacterial cells?
- How does the crowded environment of cells affect diffusion, dynamics and biochemical reactions of biomolecules?
Research areas include:
- the physicochemical properties of macromolecular complexes,
- the study of enzyme diffusion and function in the crowded environments,
- the design of ligands targeting the bacterial ribosome and mRNA,
- the thermodynamics of interactions between modified oligonucleotides,
- the delivery of peptide nucleic acid (PNA) oligomers to bacterial cells,
- coarse-grained models for proteins and nucleic acids,
- molecular dynamics simulations of proteins and RNA, including enhanced sampling methods,
- academic software development for molecular modeling and simulations as well as post-processing of trajectories.