arXiv subjects

O. O. Zdorevskyi

Publications and source records attributed to O. O. Zdorevskyi.

4 recordsLinked to original sources

arXiv2020

Interaction of hydrogen peroxide molecules with non-specific DNA recognition sites

Ion beam therapy is one of the most progressive methods in cancer treatment. Studies of the water radiolysis process show that the most long-living species that occur in the medium of a biological cell under the action of ionizing irradiation are hydrogen peroxide (H$_2$O$_2$) molecules. But the role of H$_2$O$_2$ molecules in the DNA deactivation of cancer cells in ion beam therapy has not been determined yet. In the present paper, the competitive interaction of hydrogen peroxide and water molecules with atomic groups of non-specific DNA recognition sites (phosphate groups PO$_4$) is investigated. The interaction energies and optimized spatial configurations of the considered molecular complexes are calculated with the help of molecular mechanics method and quantum chemistry approach. The results show that the H$_2$O$_2$ molecule can form a complex with the PO$_4$ group (with and without a sodium counterion) that is more energetically stable than the same complex with the water molecule. Formation of such complexes can block genetic information transfer processes in cancer cells and can be an important factor during ion beam therapy treatment.

physics.bio-ph↗

arXiv2020

Dynamics of K$^+$ counterions around DNA double helix in the external electric field: a molecular dynamics study

The structure of DNA double helix is stabilized by metal counterions condensed to a diffuse layer around the macromolecule. The dynamics of counterions in real conditions is governed by the electric fields from DNA and other biological macromolecules. In the present work the molecular dynamics study {was} performed for the system of DNA double helix with neutralizing K$^+$ counterions and for the system of KCl salt solution in the external electric field of different strength (up to 32 mV/Å). The analysis of ionic conductivities of these systems {has shown} that the counterions around the DNA double helix are slowed down compared with KCl salt solution. The calculated {values of ion mobility} are within (0.05$÷$0.4) mS/cm depending on the orientation of the external electric field relatively to the double helix. Under the electric field parallel to the macromolecule K$^+$ counterions move along the grooves of the double helix staying longer in the places with narrower minor groove. Under the electric field perpendicular to the macromolecule the dynamics of counterions is less affected by DNA atoms, and starting with the electric field values about 30 mV/Å the double helix undergoes a phase transition from double-stranded to single-strand state.

physics.bio-ph↗

arXiv2017

Possible scenarios of DNA double helix unzipping process

Analysis of single-molecule micromanipulation experiments of DNA unzipping process shows some features of the force-distance curve, namely two consequent plateaus in the area of ${\sim}12-14pN$ dependent on nucleotide sequence structure, as well as peaks appearance in the plateau area, to which it was not paid essential attention earlier. Using atom-atom potential function method the estimations of Watson-Crick base pairs opening energies are made. On the basis of this results two possible scenarios of the DNA double helix unzipping process are proposed. According to the first scenario DNA unzipping takes place slowly and as equilibrium process, with small difference between two plateaus on the unzipping curve. In this case firstly base pairs transit into the 'pre-opened' metastable state along the 'opening' pathway and then open along the 'stretch' pathway. Our estimations show that an important factor for the realization of this scenario is the existence of double-stranded DNA coil in the unopened part of DNA. The second scenario is characterized by higher opening force. In this scenario base pairs open directly along the 'stretch' pathway as non-equilibrium process. The conditions of the first scenario realization show that it can play a key role in the understanding of the DNA unzipping in vivo during transcription and genetic information transfer processes.

physics.bio-ph↗

arXiv2015

To understanding of the mechanisms of DNA deactivation in ion therapy of cancer cells

Changes in the medium of biological cell nucleus under ion beam action is considered as a possible cause of cell functioning disruption in the living body. As the most long-lived molecular product appeared in the cell after the passage of high energy ions, the hydrogen peroxide molecule is picked out. The possibility of the formation of stable complexes of hydrogen peroxide molecules with active sites of DNA nonspecific recognition (phosphate groups of the double helix backbone) is studied, and the formation of stable DNA-peroxide complexes is considered. Due to the negative charge on the oxygen atoms of DNA phosphate group in solution the counterions that under natural conditions neutralize the double helix have been also taken into consideration. The complexes consisting of oxygen atoms of DNA phosphate group, H$_2$O$_2$ and H$_2$O molecules, and Na$^{+}$ counterion have been considered. Energy of the complexes have been determined based on the electrostatic and van der Waals interactions within the approach of atom-atom potential functions. The stability of various configurations of molecular complexes has been estimated. It has been found that hydrogen peroxide molecules can form the stable complexes with phosphate groups of DNA and counterions which are no less stable than the complexes with water molecules. It is shown that the formation of stable complexes of H$_2$O$_2$--Na$^{+}$--PO$_{4}^{-}$ can be detected experimentally by the observation of specific DNA vibrations in the low-frequency Raman spectra. The interaction of H$_2 $O$_2$ molecule with phosphate group of the double helix backbone can block the processes of DNA biological functioning and induce the deactivation of the genetic apparatus of the cell. Thus, the new channel of high-energy ions action on living cell has been proposed.

physics.bio-ph↗