(67) Modelling of short DNA single strands
Date:
Contributors: Mauracher, A. , & Huber, S. E.
Venue: Multiscale Modelling of Materials and Molecules 2019, Uppsala, Sweden, June 12-14, 2019
Abstract: Radiation therapy is among the most commonly applied modalities against tumours next to chemotherapy and surgery [1]. To increase the effect of the radiation, certain therapeutic agents, i.e. radiosensitizers, are applied in combined chemoradiotherapy [2]. A review on damage of DNA labelled with electrophilic nucleobases induced by ionizing radiation summarizes the most important factors deciding about radiation damage as (i) electron affinity of the modified nucleoside, (ii) local surroundings of the label and (iii) strength of the chemical bonding between substituent and nucleobase [3]. Furthermore, radiosensitivity is also assumed to be related to hydration as well as secondary organic radicals in the cell environment [4].
For a detailed understanding of the fundamental processes governing radiosensitivity, results from both experimental studies and theoretical investigations need to be combined. From a computational point of view, the choice of an appropriate theoretical model is often a tedious task not least because of the general difficulty of finding a reasonable balance of accuracy and computational expenses. In an exploratory attempt, we present here a density functional theory study on the length dependence of some electronic properties of DNA single strands consisting of up to eight cytosine units [5]. We also study systems in which the cytosine at the 5’- or 3’-end is replaced by the anticancer agent gemcitabine. We investigate these oligonucleotides in the gas phase, as well as with Na counterions and in a polarizable continuum to model an aqueous solvent. We calculate vertical electron affinities, because the formation of a stable radical anion is considered one of the most probable steps in order to result in DNA damage [6]. Furthermore, we calculate vertical ionization energies and solvation energies. The former are important parameters for the description of electron impact ionization processes which are dominant processes for electron molecule scattering phenomena [7]. We find a pronounced odd-even oscillation for the vertical electron affinities and vertical ionization energies for all systems without counterions in the gas phase as well as in the polarizable continuum. These oscillations completely vanish by adding the Na counterions. We discuss the implications of our results with respect to comparisons between experimental and numerical investigations. For studies involving e.g. oligonucleotides, comparison of size-dependent properties derived from theory and experiment might lead to a better understanding of experimental conditions, which are sometimes difficult to determine.
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[5] A. Mauracher, S. E. Huber; ACS Omega (2019), under review.
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[7] S. E. Huber, A. Mauracher; Eur. Phys. J. D (2019), DOI: 10.1140/epjd/e2019-90708-9