Biomolecular modelling

Our research group is focused on theory and computer modelling of nucleic acid structure, dynamics and mechanical properties. We model DNA and RNA molecules at different scales, obtaining the model parameters from extensive atomic-resolution molecular dynamics simulations. We apply the results to problems from molecular biology, biophysics and nanostructure design. The group is well equipped with computer resources for simulations and data processing. We are also involved in collaborations with other laboratories in the Czech Republic and abroad. 

We are interested in two main topics.

Sequence dependent structure and stiffness of DNA. Detailed 3D structure and mechanical stiffness (elasticity, flexibility) of the DNA double helix depends on its sequence of bases. This property is used by many proteins to recognize their sequence specific DNA binding sites - the protein binds to  DNA sequences whose shape and/or stiffness are suitable for the complex formation, a mechanism called indirect readout. Our goal is to develop reliable models capable to assign shape and stiffness to a given sequence. This information can be used to predict spatial structure of a genome, binding sites of proteins and small molecules (ligands), and elastic properties of DNA nanostructures. We also want to understand the structural dynamics of DNA damaged by the UV radiation, with important applications in biomedicine.

Dynamics and mechanical properties of RNA structural motifs. RNA is structurally very rich - apart from the double helix, it folds into various non-helical motifs repeatedly used by Nature in different RNA molecules. A good example is the ribosome where stiff and flexible RNA elements work in concert with ribosomal proteins in the process of protein synthesis. The RNA motifs are also used as building blocks in the rapidly developing field of RNA nanotechnology. An advantage of RNA nanostructures is the possibility of their synthesis inside the cell, avoiding the necessity of passig through the cell membrane. Our goal is to develop suitable models and establish their parameters to describe structural dynamics and mechanical properties of important RNA motifs. This will help understand the biological function of RNA complexes such as the ribosome and rationalize the design of RNA nanostructures.