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A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide
Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456168/ https://www.ncbi.nlm.nih.gov/pubmed/36077404 http://dx.doi.org/10.3390/ijms231710007 |
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author | Santiago, João de Faria, Jhaison C. San-Miguel, Miguel Bernal, Mario A. |
author_facet | Santiago, João de Faria, Jhaison C. San-Miguel, Miguel Bernal, Mario A. |
author_sort | Santiago, João |
collection | PubMed |
description | Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indirectly by the attack of free radicals mainly produced by water radiolysis. We previously studied the impact of a proton on a DNA base pair, using the Time Dependent-Density Functional Theory (TD-DFT). In this work, we go a step further and study the attack of the OH· radical on the Guanine nucleotide to unveil how this molecule subsequently dissociates. The OH· attack on the H1′, H2′, H3′, and H5′ atoms in the guanine was investigated using the Ehrenfest dynamics within the TD-DFT framework. In all cases, the hydrogen abstraction succeeded, and the subsequent base pair dissociation was observed. The DNA dissociates in three major fragments: the phosphate group, the deoxyribose sugar, and the nitrogenous base, with slight differences, no matter which hydrogen atom was attacked. Hydrogen abstraction occurs at about 6 fs, and the nucleotide dissociation at about 100 fs, which agrees with our previous result for the direct proton impact on the DNA. These calculations may be a reference for adjusting reactive force fields so that more complex DNA structures can be studied using classical molecular dynamics, including both direct and indirect DNA damage. |
format | Online Article Text |
id | pubmed-9456168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94561682022-09-09 A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide Santiago, João de Faria, Jhaison C. San-Miguel, Miguel Bernal, Mario A. Int J Mol Sci Article Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indirectly by the attack of free radicals mainly produced by water radiolysis. We previously studied the impact of a proton on a DNA base pair, using the Time Dependent-Density Functional Theory (TD-DFT). In this work, we go a step further and study the attack of the OH· radical on the Guanine nucleotide to unveil how this molecule subsequently dissociates. The OH· attack on the H1′, H2′, H3′, and H5′ atoms in the guanine was investigated using the Ehrenfest dynamics within the TD-DFT framework. In all cases, the hydrogen abstraction succeeded, and the subsequent base pair dissociation was observed. The DNA dissociates in three major fragments: the phosphate group, the deoxyribose sugar, and the nitrogenous base, with slight differences, no matter which hydrogen atom was attacked. Hydrogen abstraction occurs at about 6 fs, and the nucleotide dissociation at about 100 fs, which agrees with our previous result for the direct proton impact on the DNA. These calculations may be a reference for adjusting reactive force fields so that more complex DNA structures can be studied using classical molecular dynamics, including both direct and indirect DNA damage. MDPI 2022-09-02 /pmc/articles/PMC9456168/ /pubmed/36077404 http://dx.doi.org/10.3390/ijms231710007 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Santiago, João de Faria, Jhaison C. San-Miguel, Miguel Bernal, Mario A. A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide |
title | A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide |
title_full | A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide |
title_fullStr | A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide |
title_full_unstemmed | A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide |
title_short | A TD-DFT-Based Study on the Attack of the OH· Radical on a Guanine Nucleotide |
title_sort | td-dft-based study on the attack of the oh· radical on a guanine nucleotide |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456168/ https://www.ncbi.nlm.nih.gov/pubmed/36077404 http://dx.doi.org/10.3390/ijms231710007 |
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