Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Santiago, João, de Faria, Jhaison C., San-Miguel, Miguel, Bernal, Mario A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784785746709708800
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
work_keys_str_mv AT santiagojoao atddftbasedstudyontheattackoftheohradicalonaguaninenucleotide
AT defariajhaisonc atddftbasedstudyontheattackoftheohradicalonaguaninenucleotide
AT sanmiguelmiguel atddftbasedstudyontheattackoftheohradicalonaguaninenucleotide
AT bernalmarioa atddftbasedstudyontheattackoftheohradicalonaguaninenucleotide
AT santiagojoao tddftbasedstudyontheattackoftheohradicalonaguaninenucleotide
AT defariajhaisonc tddftbasedstudyontheattackoftheohradicalonaguaninenucleotide
AT sanmiguelmiguel tddftbasedstudyontheattackoftheohradicalonaguaninenucleotide
AT bernalmarioa tddftbasedstudyontheattackoftheohradicalonaguaninenucleotide