(Bio)molecular Dynamics
All molecules are dynamic and even at absolute zero temperature, there is some motion preserved due to Heisenberg's uncertainty principle. The larger a molecules is, the more functionally important its motion can be and this is especially true about biomolecules. They move like Jagger. We study their choreography to understand what the biomolecules do, how they are regulated and what one can do to modulate their function to e.g. cure a dissease. Our favourite dancer is the ribosome.
Nucleic Acids
The first scientific project of Michal dealt with a DNA minor-groove binder. He was a bachelor student, a fresh member of Pavel's group, and He didn't know any single bash command. Since then, he's studied the DNA double-helix, a piece of HIV-1 untranslated mRNA, and the ribosome.
During Michal's masters, he wanted to understand what kinds of noncovalent interactions are responsible for the paradigmatic double-helical shape of DNA. The DNA can't be stabilized by inter-nucleobase hydrogen bonds. You would measure an increase of melting temperature (i.e. higher stability), if you exchanged an adenine-thymine base pair by two aromatic rings, which are unable to form hydrogen bonds (napthalenes, for instance). On the other hand, if you "switch off" stacking interactions (in a computer, of course) between nucleobases, the DNA double-helix breaks down.
Michal took a break during his PhD to return back to the nucleic acids on his Alexander von Humboldt stay focusing on non-coding RNAs. He combined the interests in halogen bonding and nucleic acids. Despite rather good electrostatic situation around NAs, only few low-molecular ligands are known to date to form halogen bonds with NAs.
He also contributed to a project of Tom Kubař. Upon certain conditions, the DNA may be ionized on a nucleobase. Such a positive charge (in blue in Figure above) may travel to large distances, so the DNA acts as a nanowire. They studied, what structural changes are induced by such charge transfer.
With Helmut, he's been working on large-scale simulations of the prokaryotic ribosome. It is a huge biomachine that produces proteins. The catalytic center is buried deep in the ribosome, so the newly synthesize protein needs to exit throught a tunnel. They've been interested in what is going on in the tunnel. The tunnel is actually highly functional environment that e.g. regulates the speed of translations, facilitates peptide (pre)folding, and acts as a binding site for many antibiotics.
Related publications
- 2018
- Molecular Simulations of the Ribosome and Associated Translation Factors
- 2017
- Reaction path averaging: characterizing structural response of the DNA double helix to electron transfer
- 2011
- On the role of London dispersion forces in biomolecular structure determination
- 2010
- Sequence-dependent configurational entropy change of DNA upon intercalation
Halogen Bonding
The halogen bond is a kind of non-covalent interaction, which involves a halogen atom (e.g. bromine) and a Lewis base (e.g. carbonyl oxygen). It means that if these two guys attract each other, we can speak about a halogen bond between them. There are two major areas, where the interest in halogen bonding has been growing terribly fast: crystal engineering and drug design.
