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.
After irradiation of cancer cells in the ion beam therapy method the concentration of hydrogen peroxide in the cell medium grows significantly. But the role of hydrogen peroxide molecules in cancer treatment has not been determined yet. We assume that interaction of peroxide molecules with DNA atomic groups can block the genetic information of the cancer cell and lead to its neutralization. To understand the possibility of DNA deactivation in the cell, in the present study the formation of complexes of hydrogen peroxide molecules with DNA specific recognition sites (nucleic bases) is considere…
A problem of inducing a required sign of chirality in a racemic mixture of enantiomers of a chiral molecule is analyzed. As an example, a racemic mixture (vapor) of left- and right-handed enantiomers of hydrogen peroxide (H2O2) molecule is considered. It is shown that biharmonic Raman excitation of the splitted due to the left-right conversion internal rotation levels can be effectively used for inducing optical activity in the initially racemic vapor of H2O2 molecules. An experiment to study this photoinduced optical rotation is discussed.
The adaptability of extremophiles on Earth raises the question of what strategies putative life might have used to adapt to the present conditions on Mars. Here, we hypothesize that organisms might utilize a water-hydrogen peroxide (H2O-H2O2) mixture rather than water as an intracellular liquid. This adaptation would have the particular advantages in the martian environment of providing a low freezing point, a source of oxygen, and hygroscopicity. The findings by the Viking experiments are reinterpreted in the light of this hypothesis. Our conclusion is that the hitherto mysterious oxidant in …
One of the most progressive methods of cancer treatment is ion beam therapy. The simulations of water radiolysis show that in the cell medium the most long-living species are hydrogen peroxide (H$_2$O$_2$) molecules. But up to the present time the role of H$_2$O$_2$ molecules in the deactivation of cancer cells has not been determined yet. To understand the possible role of H$_2$O$_2$ in ion beam therapy, the competitive interaction of H$_2$O$_2$ and H$_2$O molecules with nucleic bases in a pair on the different stages of genetic information transfer is studied in the present work. Atom-atomic…
Since Viking has conducted its life detection experiments on Mars, many missions have enhanced our knowledge about the environmental conditions on the Red Planet. However, the Martian surface chemistry and the Viking lander results remain puzzling. Non-biological explanations that favor a strong inorganic oxidant are currently favored (e.g., Mancinelli, 1989; Quinn and Zent, 1999; Klein, 1999, Yen et al., 2000), but problems remain regarding the life time, source, and abundance of that oxidant to account for the Viking observations (Zent and McKay, 1994). Alternatively, a hypothesis favoring t…
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 oxyg…
A small, bimetallic particle in a hydrogen peroxide solution can propel itself by means of an electrocatalytic reaction. The swimming is driven by a flux of ions around the particle. We model this process for the presence of a monovalent salt, where reaction-driven proton currents induce salt ion currents. A theory for thin diffuse layers is employed, which yields nonlinear, coupled transport equations. The boundary conditions include a compact Stern layer of adsorbed ions. Electrochemical processes on the particle surface are modeled with a first order reaction of the Butler-Volmer type. The …
We give unambiguous theoretical analyses and show that the exclusive biochemical reaction involved in a single nucleotide insertion into the DNA primer can be efficiently tracked using the renormalized van der Waals (vdW) interaction of a stronger type, the Hermansson blue-shifting hydrogen bond effect, and the Arunan composite hydrogen-vdW bond. We find that there are two biochemical steps involved to complete the insertion of a single base (cytosine) into the 3$'$ end of a DNA primer. First, the O3$'$ (from a DNA primer) initiates the nucleophilic attack on P$_α$ (from an incoming dCTP), in …
We present a model of proton tunnelling across DNA hydrogen bonds, compute the characteristic tunnelling time (CTT) from donor to acceptor and discuss its biological implications. The model is a double oscillator characterised by three geometry parameters describing planar deformations of the H bond, and a symmetry parameter representing the energy ratio between ground states in the individual oscillators. If the symmetry parameter takes its maximum value of 1, then we recover a known model which produced CTTs too large to be biologically relevant; but this is reduced by up to 40 orders of mag…
One of the most important topics in molecular biology is the genetic stability of DNA. One threat to this stability is proton transfer along the hydrogen bonds of DNA that could lead to tautomerisation, hence creating point mutations. We present a theoretical analysis of the hydrogen bonds between the Guanine-Cytosine (G-C) nucleotide, which includes an accurate model of the structure of the base pairs, the quantum dynamics of the hydrogen bond proton, and the influence of the decoherent and dissipative cellular environment. We determine that the quantum tunnelling contribution to the process …
Quantum theory of hydrogen atoms distribution between two complementary nucleotide bases in DNA double helix at moment of replication has been proposed in this work. It bases on two mechanisms of proton tunneling: the Andreev-Meyerovich mechanism with spontaneous phonon radiation and the Kagan-Maximov (Flynn-Stoneham) mechanism at phonon scattering. According to the presented model, the probability of proton location in shallow potential well (point mutation form) is directly proportional to temperature. It was shown that the point mutation probability decreases with increasing replication vel…
Electrical forces are the background of all the interactions occurring in biochemical systems. From here and by using a combination of ab-initio and ad-hoc models, we introduce the first description of electric field profiles with intrabond resolution to support a characterization of single bond forces attending to its electrical origin. This fundamental issue has eluded a physical description so far. Our method is applied to describe hydrogen bonds (HB) in DNA base pairs. Numerical results reveal that base pairs in DNA could be equivalent considering HB strength contributions, which challenge…
Coherent control of OH-free radicals interacting with the spin-triplet state of a DNA molecule is investigated. A model Hamiltonian for molecular spin singlet-triplet resonance is developed. We illustrate that the spin-triplet state in DNA molecules can be efficiently populated, as the spin-injection rate can be tuned to be orders of magnitudes greater than the decay rate due to small spin-orbit coupling in organic molecules. Owing to the nano-second life-time of OH free radicals, a non-equilibrium free energy barrier induced by the injected spin triplet state that lasts approximately longer t…
The radiation-induced damages in bio-molecules are ubiquitous processes in radiotherapy, radio-biology and critical to space-projects. In this study we present a precise quantification of the fragmentation mechanisms of deoxyribonucleic acid (DNA) and the molecules surrounding DNA such as oxygen and water under non-equilibrium conditions using the first-principle calculations based on density functional theory (DFT). Our results reveal the structural stability of DNA-bases and backbone that withstand up to a combined threshold of charge and hydrogen abstraction owing to simultaneous direct and…
Metropolis Monte Carlo simulation is used to investigate the elasticity of torsionally stressed double-stranded DNA, in which twist and supercoiling are incorporated as a natural result of base-stacking interaction and backbone bending constrained by hydrogen bonds formed between DNA complementary nucleotide bases. Three evident regimes are found in extension versus torsion and/or force versus extension plots: a low-force regime in which over- and underwound molecules behave similarly under stretching; an intermediate-force regime in which chirality appears for negatively and positively superc…
Understanding the damage of DNA bases from hydrogen abstraction by free OH radicals is of particular importance to reveal the effect of hydroxyl radicals produced by the secondary effect of radiation. Previous studies address the problem with truncated DNA bases as ab-initio quantum simulation required to study such electronic spin dependent processes are computationally expensive. Here, for the first time, we employ a multiscale and hybrid Quantum-Mechanical-Molecular-Mechanical simulation to study the interaction of OH radicals with guanine-deoxyribose-phosphate DNA molecular unit in the pre…
The interaction of heavy charged particles with DNA is of interest for several areas, from hadrontherapy to aero-space industry. In this paper, a TD-DFT study on the interaction of a 4 keV proton with an isolated DNA base pair was carried out. Ehrenfest dynamics was used to study the evolution of the system during and after the proton impact up to about 193 fs. This time was long enough to observe the dissociation of the target, which occurs between 80-100 fs. The effect of base pair linking to the DNA double helix was emulated by fixing the four O3' atoms responsible for the attachment. The b…
Intracellular positive ions neutralise negative charges on the phosphates of a DNA strand conferring greater strength on the hydrogen bonds that connect complementary strands into a double helix and so confer enhanced stability. Beyond a certain value of salt concentration, the DNA molecule displays a unstable nature {\it in vivo} as well as {\it in vitro}. We consider a wide range of salt concentrations and study the stability of the DNA double helix using a statistical model. Through numerical calculations we attempt to explain the different behaviour exhibited by DNA molecules in this range…
Complementary strands in DNA double helix show temporary fluctuational openings which are essential to biological functions such as transcription and replication of the genetic information. Such large amplitude fluctuations, known as the breathing of DNA, are generally localized and, microscopically, are due to the breaking of the hydrogen bonds linking the base pairs (\emph{bps}). I apply imaginary time path integral techniques to a mesoscopic Hamiltonian which accounts for the helicoidal geometry of a short circular DNA molecule. The \emph{bps} displacements with respect to the ground state …
Anomalous non-exponential relaxation in hydrated biomolecules is commonly attributed to the complexity of the free-energy landscapes, similarly to polymers and glasses. It was found recently that the hydrogen-bond breathing of terminal DNA base pairs exhibits a slow power-law relaxation attributable to weak Hamiltonian chaos, with parameters similar to experimental data. Here, the relationship is studied between this motion and spectroscopic signals measured in DNA with a small molecular photoprobe inserted into the base-pair stack. To this end, the earlier computational approach in combinatio…
Base-pockets (non-complementary base-pairs) in a double-stranded DNA play a crucial role in biological processes. Because of thermal fluctuations, it can lower the stability of DNA, whereas, in case of DNA aptamer, small molecules e.g. adenosinemonophosphate(AMP), adenosinetriphosphate(ATP) etc, form additional hydrogen bonds with base-pockets termed as "binding-pockets", which enhance the stability. Using the Langevin Dynamics simulations of coarse grained model of DNA followed by atomistic simulations, we investigated the influence of base-pocket and binding-pocket on the stability of DNA ap…
The zero point kinetic energy of protons in water is large on the scale of chemical interaction energies(29 Kj/mol in bulk room temperature water). Its value depends upon the structure of the hydrogen bond network, and can change as the network is confined or as water interacts with surfaces. These changes have been observed to be large on a chemical scale for water confined in carbon nanotubes and in the pores of xerogel, and may play a fundamental, and neglected, role in biological processes involving confined water. We measure the average momentum distribution of the protons in salmon Na-DN…
We have managed to correlate the stability constants of complex formation, which can be registered in equilibrium state, to the dynamic characteristic of the complex lifetime. Thus, the principal concept of molecular biophysics regarding biomolecule, structure-dynamics-function can be reformatted as structure-stability-function. It should be specially noted that such an approach highly simplifies end widens the time interval of investigation of dynamic characteristics of macromolecules. Study of hydration energy and hydration number by kinetic curves of water desorption from Na-DNA humidified …
We introduce a probabilistic model for protein sliding motion along DNA during the search of a target sequence. The model accounts for possible effects due to sequence-dependent interaction between the nonspecific DNA and the protein. As an example, we focus on T7 RNA-polymerase and exploit the available information about its interaction at the promoter site in order to investigate the influence of bacteriophage T7 DNA sequence on the dynamics of the sliding process. Hydrogen bonds in the major groove are used as the main sequence-dependent interaction between RNA-polymerase and DNA. The resul…
The stability and dynamics of a double-stranded DNA (dsDNA) is affected by the preferential occupancy of small monovalent molecular ions. Small metal and molecular ions such as sodium and alkyl ammonium have crucial biological functions in human body, affect the thermodynamic stability of the duplex DNA and exhibit preferential binding. Here, using atomistic molecular dynamics simulations we investigate the preferential binding of metal ion such as Na+ and molecular ions such as tetramethyl ammonium (TMA+) and 2-hydroxy-N,N,N-trimethylethanaminium (CHO+) to double stranded DNA. The thermodynam…
We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters are estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the fourteen model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction $ε_{hb}(\mathtt{AT})$ for an $\mathtt{AT}$ base pair and the ring factor $ξ$ turn out t…
Reactive oxygen and nitrogen species (ROS and RNS) play important roles in various physiological processes (e.g., phagocytosis) and pathological conditions (e.g., cancer). The primary ROS/RNS, viz., hydrogen peroxide, peroxynitrite ion, nitric oxide, and nitrite ion, can be oxidized at different electrode potentials and therefore detected and quantified by electroanalytical techniques. Nanometer-sized electrochemical probes are especially suitable for measuring ROS/RNS in single cells and cellular organelles. In this article, we survey recent advances in localized measurements of ROS/RNS insid…
The imaginary time path integral formalism is applied to a nonlinear Hamiltonian for a short fragment of heterogeneous DNA with a stabilizing solvent interaction term. Torsional effects are modeled by a twist angle between neighboring base pairs stacked along the molecule backbone. The base pair displacements are described by an ensemble of temperature dependent paths thus incorporating those fluctuational effects which shape the multisteps thermal denaturation. By summing over $\sim 10^7 - 10^8$ base pair paths, a large number of double helix configurations is taken into account consistently …
