Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Analysis of structure and thermodynamics of modified DNA duplexes using molecular dynamics simulation
Molecular dynamics (MD) simulation is an unique method for studying structure and dynamics of nucleic acid complexes. It is widely used for the investigation of conformational properties of native NA and their derivatives. High accuracy prediction of thermodynamics parameters (enthalpy, Gibbs free energy and melting temperature) for the native DNA duplex formation have been shown. The aim of this work is MD study of the structure and thermodynamic properties of nucleic acid derivatives complexes. Using the simulation parameters determined previously we have determined the conformation of the DNA duplex containing terminal spin-labeled oligonucleotides. The MD data obtained are in excellent agreement with those obtained experimentally by electronic paramagnetic resonance methods. Further we have employed these optimal simulation parameters for the analysis of thermodynamics of cooperative interaction in the nick of DNA duplex. For this purpose we determine the error of MD simulation and the length of MD trajectory that would be enough to obtain reliable values of cooperative interaction energies. Then, the values of enthalpy for a series of cooperative contacts in the nick have been obtained experimentally (via DNA melting) and by MD simulation. The data from the two methods are in a good agreement, although the MD data are somewhat less sequence dependent than the experimental one.
At the next stage we have studied the influence of non-nucleotide insert based on dietheleneglycol phosphodiester "bridged" oligonucleotides) [2, 3] on conformational and thermal stability. It was found, that local duplex structure perturbation leads to bending of the double helix as was observed experimentally . The thermodynamic effect of the DNA modification calculated from the melting data is also close to the value obtained via MD, again, with low sequence dependence in the case of MD. Now we begin to study complexes of morpholine NA analogues with non-modified nucleic acids. The first results of MD simulations show good perspectives for reliable prediction of thermodynamics for such chimeric complexes.
This research has been supported by grants of RFBR (13-04-01176-a) and the Russian Government (14.B25.31.0028).
Pyshnyi, D.V., Lomzov, A.A., Pyshnaya, I.A., Ivanova, E.M. (2006). Hybridization of the bridged oligonucleotides with DNA: thermodynamic and kinetic studies. J Biomol Struct Dyn. 23(5), 567-580.
Lomzov, A.A., Pyshnaya, I.A., Ivanova, E.M., Pyshnyi, D.V. (2006). Thermodynamic parameters for calculating the stability of complexes of bridged oligonucleotides. Dokl. Biochem. Biophys. 409, 211-15.
Vinogradova, O.A., Eremeeva, E.V., Lomzov A.A., Pyshnaia, I.A., Pyshnyi, D.V. (2009). Bent dsDNA with defined geometric characteristics in terms of complexes of bridged oligonucleotides. Russian J. Bioorg. Chem. 35, 349-359.