Our research interests involve studying the function, dynamics, and physico-chemical properties of nanoscale assemblies to understand their activities in the cell to be able to inhibit these activities by small molecules, peptides or short oligonucleotide mimics.
For many years we have focused on aminoglycoside antibiotics that target the RNA of the bacterial ribosome, which is the macromolecular complex responsible for protein synthesis in the cell. We have been also interested in other non-coding bacterial RNAs and their inhibition by anti-sense modified oligonucleotides. We have been investigating the use of peptide nucleic acids as inhibitors of bacterial RNA, and looking for carriers of peptide nucleic acids to bacterial cells. One of such carriers that we have found is vitamin B12. Another area of our interest are proteases, especially viral ones. We are investigating how macromolecular crowding affects the dynamics and enzymatic activities of various proteases. We combine theoretical approaches (computational simulations and molecular modeling) with experimental biophysical measurements (absorbance, fluorescence, circular dichroism spectroscopy, isothermal titration calorimetry) and microbiology.
With the aim of targeting bacteria with aminoglycosides, membrane-active peptides and modified oligonucleotides, we have been asking the following questions:
- How to improve aminoglycoside antibiotics?
- How to design effective antibacterial peptides?
- How to find good cellular targets for antibacterial peptide nucleic acids?
- How to deliver peptide nucleic acid oligomers to bacterial cells?
- How the crowded environment of the cells affects diffusion, dynamics and biochemical reactions of biomolecules?
Research areas include:
- physicochemical properties of macromolecular complexes,
- enzyme diffusion and function in the crowded environments,
- design of ligands targeting the bacterial ribosome and mRNA,
- thermodynamics of interactions between modified oligonucleotides,
- 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.