Theoretical analysis of the effects of guanine oxidative damage on the properties of B-DNA telomere fragments |
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Authors: | Piotr Cysewski Przemysław Czeleń |
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Institution: | (1) Physical Chemistry Department, Collegium Medicum, Nicolaus Copernicus University, Kurpińskiego 5, 85-950 Bydgoszcz, Poland;(2) Faculty of Chemical Technology and Engineering, General Chemistry Department, University of Technical and Agriculture, Seminaryjna 3, 85-326 Bydgoszcz, Poland |
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Abstract: | 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.
Figure The consequences of guanine oxidation in central GGG telomeric triad on electrostatic properties of CCGTACTT-A1G2G3G4T5T6-AGGGTT-AACA telomere fragment
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | B-DNA 8-oxo-guanine GGG triad Molecular modeling Oxidative damage Telomers |
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