  The oxidative damage of DNA is a compelling issue in molecular biophysics as
it plays a vital role in the epigenetic control of gene expression and is
believed to be associated with mutagenesis, carcinogenesis, and ageing. To
understand the microscopic structural changes in physical properties of DNA and
the resulting influence on its function due to oxidative damage of its
nucleotide bases, we have conducted all-atom molecular dynamic simulations of
double-stranded DNA (dsDNA) with its guanine bases being oxidized. The guanine
bases are more prone to oxidative damage due to the lowest value of redox
potential among all nucleobases. We have analyzed the local as well as global
mechanical properties of native and oxidized dsDNA and explained those results
by microscopic structural parameters and thermodynamic calculations. Our
results show that the oxidative damage of dsDNA does not deform the
Watson-Crick geometry; instead, the oxidized DNA structures are found to be
better stabilized through electrostatic interactions. Moreover, oxidative
damage changes the mechanical, helical, and groove parameters of dsDNA. The
persistence length, stretch modulus, and torsional stiffness are found to be
48.87 nm, 1239.26 pN, and 477.30 pN.nm^2, respectively, for native dsDNA, and
these values are 61.31 nm, 659.91 pN, and 407.79 pN.nm^2, respectively, when
all the guanine bases of the dsDNA are oxidized. Compared to the global
mechanical properties, the changes in helical and groove properties are found
to be more prominent, concentrated locally at the oxidation sites, and causing
the transition of the backbone conformations from BI to BII at the regions of
oxidative damage.
