Theoretical analysis of the effects of guanine oxidative damage on the properties of B-DNA telomere fragments.

The molecular dynamics as well as ab initio MP2/6-31G(d = 0.25) single point calculations were performed for native and oxidized B-DNA telomeric fragments. The structural, dynamic, energetic and electrostatic properties along with frontier orbitals distribution were described for the central triad consisting of three guanine molecules in its canonical or oxidized forms. Although the average structural parameters characterizing all of the studied telomere fragments are close each to other, the significant consequence on angular and displacement flexibilities are observed. Namely, the increase of mutual displacement of two successive base pairs along either axis and increase of the rotation of two bases of opposite strand are main dynamic consequences of presence of 8-oxo-guanine in the central triad of telomeric B-DNA. Besides, the significant increase of stacking energies in case of 8-oxo-guanine were found. Furthermore, the guanine pattern visible from the major groove may be described as donor-acceptor-acceptor formed by H8-N7-O6 atoms, respectively. To the contrary the presence of 8-oxo-guanine changes the electrostatic properties of the major groove into acceptor-donor-acceptor coming from O8-H7-O6 atoms. This results in significant alteration of ESP characteristics. Finally, the molecular orbital properties are also significantly affected by oxidation of telomeric B-DNA fragments. All these factors contribute to decrease of binding of telomere proteins.