Laboratory of Structural Chemistry of Nucleic Acids
Institute of Bioorganic Chemistry of the Polish Academy of Sciences
Noskowskiego 12/14, PL-61-704 Poznan
Presentation of my research and publications
In years 1995-2008, my work (which was documented in my PhD thesis and more than a dozen of publications) has concentrated mostly on conformational analysis of short modified DNA duplexes and various RNA domains, in order to evaluate the influence of non-standard structural elements on the local and global molecules conformation using various strategies of molecular mechanics and molecular dynamics simulations as well as a variety of procedures for structural analysis and visualization of the results. The simulations were based on the Amber forcefield and I used: InsightII, Discover, Gaussian, Resp and AMBER programs for various stages of modeling. During my postdoctoral fellowship in the Prof. Eric Westhof's laboratory in Strasbourg, I researched the model of the 5S rRNA loop E under various ionic conditions in order to understand the stabilizing role of di- and monovalent cations, as well as their binding characteristics [14,15].
A considerable amount of my efforts was devoted to creating procedures and strategies for optimizing the molecular dynamics simulation protocol, as well as for better evaluation and visualization of results. The most important strategies developed concern monitoring of the stacking interactions within the nucleic strands [2,8] as well as cluster analysis applied for evaluating the internal conformational similarity within the trajectories  (program SAHN). Currently, I am interested in investigating the possible improvement of the MD protocol by alternate heating and cooling of the model ("Molecular Dynamics Thermocycler" ).
Another topic I dealt with was the influence of single modified residues introduced into a DNA duplex on its global and local structure. I have acquired interesting molecular dynamics results [7,8] for alpha-anomerized deoxynucleotides in respect to their base pairing and overall duplex stability.
In the last years my work concerned molecular dynamics simulation and conformational analysis of RNA molecules containing single-stranded regions. The model molecules I focused on were RNA duplexes containing trinucleotide adenosine bulges [2,3,4,10] and molecules derived from the HIV-1 TAR RNA system. One of the points of interest in my research has been the influence of modification of purine residues to 2-aminopurine on the conformational dynamics of a bulged RNA region. Because 2-aminopurine is used as a blue fluorescent probe for nucleic acids structural research, it is interesting to evaluate its behavior within the nucleic acid molecule. The results suggest that in case of adenine, this modification has only a negligible effect on the overall RNA conformation[2,5], while 2-aminopurine is incapable of mimicking a guanine residue . A related study concerned the possibility of magnesium cation binding to the TAR RNA bulge loop [6,11]. The data obtained so far indicate several possible binding sites within the bulge region. These results are in contradiction to the present 19F NMR data which do not suggest Mg2+ binding to that molecule.
An interesting issue I also focus on is the RNA hydration pattern, especially within the single-stranded regions . Our results indicate a noticeable correlation between the conformation of those areas and the hydration of certain atoms within them. This supports the notion of water as an integral part of the RNA structure.
Comments, remarks or questions
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