Protection of DNA against low-energy electrons by amino acids: a first-principles molecular dynamics study

Gu, Bing-Lin; Smyth, Maeve; Kohanoff, Jorge

doi:10.1039/c4cp03906h

Cited by 24 publications

(30 citation statements)

References 43 publications

(78 reference statements)

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“…Consequently, raising the free-energy barrier associated with strand breaks, prompted by these mechanisms, can halt further reactions of the excess electron within the strand of DNA, for instance, transferring the electron to the backbone which leads to induce a strand break in DNA. Increasing the ratio of amino acid to nucleic acid will enhance the protecting role of amino acids, and accordingly will decrease the induction of DNA strand breaks by LEEs, as shown experimentally [137,139].…”

Section: Lees Interaction With Protein Building Blocksmentioning

confidence: 99%

“…Furthermore, by studying via first-principles molecular dynamics simulations a model system composed of thymine and glycine, Kohanoff et al [139] recently investigated the protection of DNA by amino acids against the effects of LEEs. They considered thymine-glycine dimers and a condensed-phase model consisting of one thymine molecule solvated in amorphous glycine.…”

Section: Lees Interaction With Protein Building Blocksmentioning

confidence: 99%

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Transient Anions in Radiobiology and Radiotherapy: From Gaseous Biomolecules to Condensed Organic and Biomolecular Solids

Alizadeh¹,

Ptasińska²,

Sanche³

2016

Radiation Effects in Materials

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This chapter focuses on the fundamental processes that govern interactions of lowenergy (1-30 eV) electrons with biological systems. These interactions have been investigated in the gas phase and within complex arrangements in the condensed phase. They often lead to the formation of transient molecular anions (TMAs), and their decay by autoionization or dissociation accompanied by bond dissociation. The damage caused to biomolecules via TMAs is emphasized in all sections. Such damage, which depends on a large number of factors, including electron energy, molecular environment, and type of biomolecule, and its physical and chemical interactions with radiosensitizing agents are extensively discussed. A majority of recent findings resulting from experimental and theoretical endeavors are presented. They encompass broad research areas to elucidate important roles of TMAs in irradiated biological systems, from the molecular level to nanoscale cellular dimensions. Fundamental aspects of TMA formation are stressed in this chapter, but many practical applications in a variety of radiation-related fields such as radiobiology and radiotherapy are addressed.

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Section: Lees Interaction With Protein Building Blocksmentioning

confidence: 99%

Section: Lees Interaction With Protein Building Blocksmentioning

confidence: 99%

Transient Anions in Radiobiology and Radiotherapy: From Gaseous Biomolecules to Condensed Organic and Biomolecular Solids

Alizadeh¹,

Ptasińska²,

Sanche³

2016

Radiation Effects in Materials

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“…The most popular multi‐level approach is QM/MM method, where the solute is treated using QM, and the surrounding water molecules are treated with molecular mechanics (MM). A limited number of QM/MM based explicit solvation studies on the electron attachment to the genetic material has been reported in recent times. However, they are mostly restricted to nucleobases.…”

Section: Introductionmentioning

confidence: 99%

Interactions of Solvated Electrons with Nucleobases: The Effect of Base Pairing

2020

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We have investigated the effect of base pairing on the electron attachment to nucleobases in bulk water, taking the guanineÀ cytosine (GC) base pair as a test case. The presence of the complementary base reinforces the stabilization effect provided by water and preferentially stabilizes the anion by hydrogen bonding. The electron attachment in bulk-solvated GC happens through a doorway mechanism, where the initial electron attached state is water bound, and it subsequently gets converted to a GC bound state. The additional electron in the final GC bound state is localized on the cytosine, similar to that in the gas phase. The transfer of the electron from the initial water-bound state to the final GC bound state happens due to the mixing of electronic and nuclear degrees of freedom and takes place at a picosecond time scale.[a] Dr.

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“…In addition the hydrogen-bonding interactions may play an essential role in quenching SSB through the stabilization of the anionic species. These hypotheses were successively tested via FPMD simulations of a single thymine in a bath of 32 glycine molecules instead of water [147]. These were fully quantum simulations at the DFT-PBE level and TZVP-MOLOPT basis set.…”

Section: Amino Acidsmentioning

confidence: 99%

Interactions between low energy electrons and DNA: a perspective from first-principles simulations

Kohanoff¹,

McAllister²,

Tribello³

et al. 2017

J. Phys.: Condens. Matter

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Abstract. DNA damage caused by irradiation has been studied for many decades. Such studies allow us to better assess the dangers posed by radiation, and to increase the efficiency of the radiotherapies that are used to combat cancer. A full description of the irradiation process involves multiple size and time scales. It starts from the interaction of radiation -either photons or swift ions -with the biological medium. Such interactions cause electronic excitation and ionisation. The two main products of ionising radiation are thus electrons and radicals. Both of these species can cause damage to biological molecules, in particular DNA. In the long run, this molecular level damage can prevent cells from replicating and can hence lead to cell death. For a long time it was assumed that the main actors in the damage process were the radicals. However, experiments in a seminal paper by the group of Leon Sanche in 2000 showed that low-energy electrons (LEE), such as those generated when ionising biological targets, can also cause bond breaks in biomolecules, in particular strand breaks in plasmid DNA [1]. These results prompted a significant amount of experimental and theoretical work aimed at elucidating the role played by LEE in DNA damage.In this Topical Review we provide a general overview of the problem. We discuss experimental findings and theoretical results hand in hand with the aim of describing the physics and chemistry that occurs during the process of radiation damage, from the initial stages of electronic excitation, through the inelastic propagation of electrons in the medium, the interaction of electrons with DNA, and the chemical end-point effects on DNA. A very important aspect of this discussion is the consideration of a realistic, physiological environment. The role played by the aqueous solution and the amino acids from the histones in chromatin must be considered. Moreover, thermal fluctuations must be incorporated when studying these phenomena. Hence, a special place in this Topical Review is occupied by our recent first-principles molecular dynamics simulations that address the issue of how the environment favours or prevents LEEs from causing damage to DNA. We finish by summarising the conclusions achieved so far, and by suggesting a number of possible directions for further study.

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Protection of DNA against low-energy electrons by amino acids: a first-principles molecular dynamics study

Cited by 24 publications

References 43 publications

Transient Anions in Radiobiology and Radiotherapy: From Gaseous Biomolecules to Condensed Organic and Biomolecular Solids

Transient Anions in Radiobiology and Radiotherapy: From Gaseous Biomolecules to Condensed Organic and Biomolecular Solids

Interactions of Solvated Electrons with Nucleobases: The Effect of Base Pairing

Interactions between low energy electrons and DNA: a perspective from first-principles simulations

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