Abstract

Molecular dynamics study of OH radical-mediated DNA damage production

This study focuses on the temporary increase in permeability of a protocell membrane. Membrane permeability is an important property related to the uptake of molecules from the environment and the retention of internally synthesized functional polymers. Vesicles composed of fatty acids are often employed as a protocell model. Although Mg²⁺ is important for non-enzymatic RNA synthesis, it has been reported that the permeability of fatty acid vesicles is increased by Mg²⁺, and furthermore, at concentrations above a certain level, the molecules encapsulated in vesicles leak out. However, the mechanism by which the membrane becomes unstable has not yet been elucidated. We analyzed the structural changes in fatty acid bilayers induced by Mg²⁺ addition using molecular dynamics simulations. The results show that Mg²⁺ does not cause defects in fatty acid flat membranes, but rather causes them to pack tightly. This suggests that the curvature of the lipid bilayer may be important for defect formation on fatty acid vesicles.

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Molecular dynamics study of defects on fatty acid vesicle induced by magnesium ion

This study focuses on the temporary increase in permeability of a protocell membrane. Membrane permeability is an important property related to the uptake of molecules from the environment and the retention of internally synthesized functional polymers. Vesicles composed of fatty acids are often employed as a protocell model. Although Mg²⁺ is important for non-enzymatic RNA synthesis, it has been reported that the permeability of fatty acid vesicles is increased by Mg²⁺, and furthermore, at concentrations above a certain level, the molecules encapsulated in vesicles leak out. However, the mechanism by which the membrane becomes unstable has not yet been elucidated. We analyzed the structural changes in fatty acid bilayers induced by Mg²⁺ addition using molecular dynamics simulations. The results show that Mg²⁺ does not cause defects in fatty acid flat membranes, but rather causes them to pack tightly. This suggests that the curvature of the lipid bilayer may be important for defect formation on fatty acid vesicles.

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Study on effect of oxygen concentration in water radiolysis using Geant4-DNA

The effect of the presence of dissolved molecular oxygen in water radiolysis was studied using a Geant4-DNA Monte Carlo simulation. The simulation included physics and chemistry processes, in which 72 chemical reaction channels were registered including reactions of dissociated molecules with dissolved oxygen in water. In order to verify the chemical reactions, time dependent yields of OH radical and e_aq^- by 5 MeV proton irradiation were calculated for two different oxygen concentrations. In addition, time dependent yields of several molecular species by 4.5 keV electron irradiation were calculated to study a production of O₂^- and HO₂ radicals, which is hypothesized to be linked to the oxygen sensitization effect in biological systems.

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Reactive molecular dynamics study on intermolecular structural changes of hydrogen-abstracted polyethylene chains

One of the effects that radiation causes on polymeric materials is the hydrogen abstraction reaction, which induces radicalization and the subsequent structural changes such as disorder of structure, cross-link and chain scission. However, at a nanoscale, the changes of the entire chain and the reaction paths on local segments are difficult to be independently and completely caught by experiment. In our former reactive molecular simulations, we observed structural disruption, formation of C=C double bond, cyclic structure and conjugated bond, and chain scission. In this research, we investigate the structural changes of hydrogen-removed polyethylene by means of reactive molecular dynamics simulations using one of ReaxFF force field parameter sets, called CHO-2006.

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Molecular dynamics study of microscopic mechanism of OH radical-induced DNA damage

The backbone of DNA has sugars joined by phosphodiester bonds. Highly reactive hydroxyl (OH) radicals are produced by ionizing radiation in a cell, which can abstract any hydrogen atoms from DNA. Carbon centerd sugar radicals produced by the hydrogen abstraction from sugar moiety triggers a common lesion, single-strand break which induces disease such as carcinogenesis. However, the abstraction mechanisms at the molecular level remain unsolved. Thus, we employed molecular dynamics simulations on hydroxyl radicals around DNA to evaluate their accessibility to hydrogen atoms on sugar moiety. In particular, we introduced restraining potentials on the hydroxyl radicals, which enabled us to sufficient sampling of the hydroxyl radicals to each hydrogen atom on DNA. Our simulation results were very different from those reported previously. This indicates that the conventional evaluations based on the solvent-accessible surface area or the water accessibility are needed to be modified.

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Evaluation tolerance of DNA damaged by tritium beta decay using MD simulation

In order to quantitatively elucidate the effect of tritium β decay in MD simulations, the initial structure of DNA must be stabilized under human body conditions with ReaxFF, which can handle covalent bonds. The arrangement of counterions around DNA plays an important role in the stable structure of DNA. Therefore, focusing on the arrangement of sodium ions in the system, we performed simulations in which sodium ions move to a position where they can shield the charge of the DNA. As a result, we were able to create a stable DNA structure that could be used to simulate tritium decay effects.

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Atomistic analysis of strand breaks of DNA in tritiated water using Geant4-DNA simulation

The strand breaks in a double strand B-form DNA in tritiated water were studied using Geant4-DNA simulation. The purpose of this study is to establish an analysis scheme for evaluating strand breaks with atomistic structure of DNA. The simulations were performed in homogeneous water, and strand breaks were estimated by superimposing the interaction points on the atomistic structure of DNA. The results were evaluated in terms of the yield ratio of single strand breaks (SSBs) to double strand breaks (DSBs), the contribution of the direct and the indirect effects to SSB and DSB, and the reaction probability of hydroxyl radical by abstraction of hydrogen atom in DNA.

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Molecular dynamics simulation of water dynamics in zwitterionic polymer brush-water interface

All-atom molecular dynamics simulations of zwitterionic polymer brushes in water were performed to determine the effect of the tacticity of the polymer brush on the interfacial water dynamics. Our simulations show that syndiotactic and isotactic zwitterionic polymer brushes have different chain shapes and water dynamics. The hydrogen bond lifetimes of the syndiotactic model were found to be longer than those of the isotactic model. These results actually confirm that there are differences in the dynamics of interfacial water depending on the tacticity of the polymer brush.

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Evaluation of solvent-accessible surface area of back- bone hydrogen in telomeric DNA for studying tritium resistance of DNA

Tritiated water is generated under the decommissioning process of the Fukushima Daiichi Nuclear Power Station. In addition, tritium is planning to use as fuel in fusion power plants, which is expected as a future power generation technology. Therefore, it is important to understand the impact of tritium on biomolecules in living organisms including human in detail. We aim to elucidate the mechanism of DNA damage due to the radioactive decay effect that occurs when light hydrogen in human DNA is replaced with tritium, using molecular dynamics (MD) methods. To understand the decay effect on DNA, first, it is necessary to evaluate the replaceability of light hydrogen to tritium for each hydrogen in DNA. In this study, to evaluate the degree of replaceability of the backbone hydrogen atoms in telomeric DNA of human, solvent-accessible surface area (SASA) is calculated for the data obtained by MD simulation. As a result, it is found that the SASA of H5 hydrogen is large in the hydrogen atoms in the backbone.

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Molecular dynamics simulation and numeric calculation of a damaged polyethylene assuming tritium substitution and decay

It is important to simulate how the structure of a molecule, such as DNA, responds when subjected to tritium substitution and decay. This is because structural changes in DNA can inhibit enzymatic repair. We have observed the response of single-stranded polyethylene, a simpler polymer, by molecular dynamics simulations and attempted to make theoretical predictions based on non-equilibrium statistical mechanics. As a result, we found that we could predict the response to some extent for low damage rates.

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Molecular Dynamics Study of Water Dynamics in Zwitterionic Polymer Brush-Water Interface

Polymer brushes have a protein antifouling effect to a biomaterial in vivo. The dynamics of water in polymer brush-water interface is studied by the molecular dynamics simulations to clarify the molecular mechanism of the protein antifouling effect. In addition, we also clarify the relationship between the structural characteristics of polymer brushes and the dynamics of water.

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Reactive molecular dynamics study on damaged polyethylene after hydrogen abstraction by radiation

One of the effects that radiation causes on polymeric materials is the hydrogen abstraction reaction, which induces radicalization and the subsequent structural changes such as de-crystallization, cross-link and chain scission. However, at a nanoscale, the changes of the entire chain and the reaction paths on local segments are difficult to be completely caught by experiment. In this research, we investigate the structural change of hydrogen-removed polyethylene by means of reactive molecular dynamics simulations using two kinds of ReaxFF force field parameter sets, called CHO-2006 and CHO-2016. And to compare the two parameter sets, atomic forces of the final configurations are calculated by density functional theory. Our results suggest that CHO-2006 is a better parameter set for treating damaged hydrocarbons. Furthermore, during simulations using the CHO-2006 parameter set, de-crystallization, formation of C=C double bond, cyclic structure and conjugated bond and chain scission were observed.

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The study on the stability of DNA structure by steered molecular dynamics simulations

The stability of DNA double-stranded structure is examined by pulling atoms using steered molecular dynamics (SMD) simulations. We use the base sequence bounded by helicase which acts to separate double-stranded chain into single-stranded one, in addition to sequences of adenine-thymine (AT) pairs only and guanine-cytosine (GC) pairs only. As we expected, the DNA fragment with the helicase binding sequence needs the lowest work for separating chains. However, we obtained an unexpected result that the fragment with the sequence of AT pairs only needs the highest work for separating two chains, though it has smallest number of hydrogen bonds.

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Effect of tritium beta decay in deoxy-D-ribose on duplex of telomeric DNA

We confirm the relationship between the number of tritium substitutions for hydrogen in DNA and the occurrence of double strand breaks (DSBs) by using MD simulation. As the result, to induce DSB by the decay effect, it is necessary to damage the DNA with a large number of decays.

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Tritium-induced damage on polymers and biopolymers: Molecular dynamics simulations and theoretical calculations

Molecular dynamics (MD) simulations and theoretical calculations are carried out to study the tritium-induced damage of polymers and biopolymers. We deal with several topics related to the tritium-induced damage: (i) MD simulations of structural change of polymers and DNA by decay effect in which chemical bonds break by beta decay of substituted tritium to helium-3, (ii) MD simulations of structural change of DNA by indirect action in which tritiuminduced or radiation-induced hydroxyl radicals damage DNA, and (iii) theoretical calculations of structural change of polymers by decay effect based on the linear response theory. In this paper, we briefly introduce these results.

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Rate of double strand breaks of genome-sized DNA in tritiated water: dependence on tritium concentration, water temperature, and DNA concentration

A simple experimental system to examine the rate of double strand breaks of genome-sized DNA molecules in tritiated water under well-controlled conditions was established for the validation of computer simulation on interactions of biomolecules and ionizing radiation. No noticeable irradiation effects were observed at tritium concentration of 1300 Bq/cm³, indicating that the effects of β-ray irradiation was far smaller than those of oxidation and/or thermal motion at the low dose rate (43 μGy/h). Radiation-induecd double-strand breaks (DSBs) were clearly recognizable at tritium concentrations of 4.0-5.2 MBq/cm³. The dependence of DSB rate on water temperature and DNA concentration was examined by using the high concentration tritiated water.

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Linear response theory applied to molecular dynamics simulations

We show that the linear response theory is applicable to molecular dynamics simulations in which sudden change in an external force plays a role for relaxation of a system. As one of such systems, we focus on the structural change of tritium-substituted polyethylene induced by beta decays of substituted tritium, and derive the time derivative of the dynamical quantity, which is conjugate to the force applied as perturbation in the framework of the linear response theory, required to calculate the response function.

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Molecular Simulation for Soft and Hard Matters

We introduced our three simulation studies of molecular dynamics (MD) simulation and dissipative particle dynamics (DPD) simulation in order to reveal the motion of the atoms or molecules. The first MD simulation result shows that short chain molecules forms domain structure by the Lennard-Jones interaction, and the domain interacts with each other like rigid-body. The other MD simulation gives the information of the graphite erosion when hydrogen atoms are irradiated to graphite. Finally, using DPD simulation, we obtained the structure formation of amphiphilic molecules.

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Molecular dynamics study of new phase transition in supercooled cyclohexane

A recent experimental result revealed that a first-order phase transition occurs in supercooled cyclohexane confined in nanopores. This transition is suggested to be a liquidliquid phase transition. To understand the nature of this transition, we performed all-atom molecular dynamics simulations of supercooled cyclohexane, and the local structures in cyclohexane were analyzed using Voronoi tessellation technique. It is found that icosahedral structures often appear in the supercooled and glassy state. As the temperature decreases, the fraction of icosahedral structures increases at first, but the increase stops around T=170K. This temperature is above the glass transition temperature, which implies some structural change occurs in the supercooled state. Our findings would be useful for understanding the mechanism of a liquid-liquid phase transition.

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Molecular Dynamics Simulations of One-, Two-, Three-dimensional Hopping Dynamics

Hopping dynamics in liquid crystal phases and thermodynamic metastable states are investigated by constant pressure and temperature molecular dynamics simulations. In systems of monodisperse WCA soft spheres, we identify ten new states in addition to those already reported. Combinations of different physical properties clearly show they are distinctive states of glassy free-energy minima.

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Shape transition of micelles in amphiphilic solution: A molecular dynamics study

The shape transition of micelles in an amphiphilic solution is studied by a molecular dynamics simulation of coarse-grained rigid amphiphilic molecules with explicit solvent molecules. Our simulations show that the micellar shape changes from a disc into a cylinder, and then into a sphere as the hydrophilic interaction increases. We find that the potential energy decreases monotonically even during the micellar shape transition as the hydrophilic interaction increases. In contrast, it is ascertained that there exists a wide coexistence region in the intensity of the hydrophilic interaction between a cylinder and a sphere.

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Optimization of a corrugated millimeter-wave waveguide and a miter bend by FDTD simulation

We estimate the transmission efficiency of the electromagnetic wave through the system composed of waveguide and miter bend by Finite-Difference Time-Domain (FDTD) simulation. As the fisrt approach of this estimation, we choose the case that the input wave is TE₁₁ mode. In this case, the efficiency is estimated as 99.65 % for the system without grooves and 76.48 % for the system with grooves (which is called as "corrugate"). Comparing the distributions of the input electric field with that of the output electric field, the effect of the grooves is found as follows: Because the TE₁₁ mode has an anisotropy, its shape is changed by the miter bend. This property appears in the corrugated system more strongly than the non-corrugated system.

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FDTD simulation of millimeter-wave corrugated waveguides with cylindrical symmetry model

The purpose of this study is to calculate the relationship between the circular shape of a corrugated waveguide and its electrical transfer characteristics by the finite-difference timedomain (FDTD) method. To improve the waveguide to transport with a lower loss of energy than the previous design, we optimize the waveguide structure by the time evolution of the electromagnetic fields in the waveguide. However, the calculation in a 3D model is difficult because of the large data size and the long calculation run time. Therefore, we used a cylindrical symmetry model. As a result of this simulation, a correlation of the electromagnetic field in the input source position and the output position has been calculated.

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