The mechanism of DNA deactivation by hydrogen peroxide action

1. The mechanism of DNA deactivation by hydrogen peroxide action

13th Greta Pifat Mrzljak International School of Biophysics
The mechanism of DNA
deactivation by hydrogen
peroxide action
Oleksii O. Zdorevskyi, Sergey N. Volkov
Bogolyubov Institute for Theoretical
Physics of the NAS of Ukraine
Datum&&&

2.

3.

Mechanisms of DNA
deactivation
Free radicals
Secondary
electrons
Solov’yov A. V., Surdutovich E., Scifoni E., Mishustin I.,
Greiner W., Phys. Review. E 79, 011909 (2009)
Structural changes
of the medium?

4. Hydrogen peroxide molecule

The roal of H2O2
molecules in the
ion beam
therapy?

5. DNA macromolecule structure

H2O
H2O2
Na+
PO4

6. Atom-atomic potential function method

Energy of the complex
U U VdW (rij ) U BM (rij ) U HB (rij )
i, j
Wan-der-Waals
interaction
(Lennard-Jones
potential)
U VdW (rij )
Aij
rij6
H-bond consideration
Bij
rij12
U HB (rij )
Aij(10 )
10
ij
r
Bij(10 )
rij12
Electrostatic interaction (BornMayer potential)
brij
r0 rij
U BM (rij )
1 - 2 exp
4 0 rij r0
b
qi q j

7. Potential parameters

Interaction
vdW
H-bond
Parameter
O-O
O-H
O-H
Aij (Å6 kcal/mol)
200
86
3,76*103(Å10 kcal/mol)
Bij(Å12 kcal/mol) 12900 31300
9,7*103(Å12 kcal/mol)
Zhurkin V. B., Poltev V. I., Florentiev V. L., Mol. Biol. 14,
1116 (1980)

8. H2O2 molecule with DNA phosphate group

9. Two-component complexes

Necessity of trial
complexes
consideration

10. Three-component complexes

11. Low-frequency DNA vibration spectrum

D.V. Pyatnytskyi, O.O.
Zdorevskyi, S.M.
Perepelytsya,
S.N.Volkov, EPJ D, 2015
Arrhenius lifetime equations
H 2O2 H 2O

12. Conclusions

Changes to the life cell medium structure as a result of ionizing radiation
action is analyzed. Dominant role of hydrogen peroxide molecule in this
process is determined.
Binding energies of complexes of DNA phosphate group with different
molecules are estimated. It is determined that hydrogen peroxide in the
presence of sodium counterion can form stable complex with DNA
phosphate group.
Vibration frequencies and living times of these complexes are estimated.
It is determined that complex H2O2-DNA is more long-living than the
complex H2O-DNA.
It is determined that hydrogen peroxide molecules can form a stable longliving complex with DNA which blocks the process of protein-nucleic
recognition and genetic information transition. This may be a key
mechanism in the ion therapy treatment.

13. Thank you for your attention!