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Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations

The structural and energetic properties of native and oxidized telomeric complexes were defined by means of molecular dynamic (MD) simulations. As a starting point, the experimental conformation of B-DNA d(GpTpTpApGpGpGpTpTpApGpGpG) oligomer bound to human protein telomeric repeat binding factor 1 (...

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Autores principales: Czeleń, Przemysław, Cysewski, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713266/
https://www.ncbi.nlm.nih.gov/pubmed/23674370
http://dx.doi.org/10.1007/s00894-013-1859-z
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author Czeleń, Przemysław
Cysewski, Piotr
author_facet Czeleń, Przemysław
Cysewski, Piotr
author_sort Czeleń, Przemysław
collection PubMed
description The structural and energetic properties of native and oxidized telomeric complexes were defined by means of molecular dynamic (MD) simulations. As a starting point, the experimental conformation of B-DNA d(GpTpTpApGpGpGpTpTpApGpGpG) oligomer bound to human protein telomeric repeat binding factor 1 (TRF1) was used. The influence on the stability of the telomeric complex of the presence of 8-oxoguanine (8oxoG) in the central telomeric triad (CTT) was estimated based on trajectories collected during 130 ns MD runs. The data obtained indicate that the system analyzed is highly sensitive to the presence of oxidative damage in the CTT of the B-DNA telomeric sequence. The most important changes were observed in the immediate vicinity of the 8-oxoguanine molecule. The significantly higher mobility of arginine 425 interacting directly with the oxidized guanine molecule has a large influence on the structural, dynamic and energetic properties of neighboring amino acids. Local changes observed for individual hydrogen bonded interactions localized in the major groove of B-DNA also have significant impact on the properties of hydrophobic clusters, which are the second type of force responsible for stability of the studied bio-system. All the changes reported in detail here unambiguously indicate a significant decrease in telomer binding affinity after oxidation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-013-1859-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-37132662013-08-15 Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations Czeleń, Przemysław Cysewski, Piotr J Mol Model Original Paper The structural and energetic properties of native and oxidized telomeric complexes were defined by means of molecular dynamic (MD) simulations. As a starting point, the experimental conformation of B-DNA d(GpTpTpApGpGpGpTpTpApGpGpG) oligomer bound to human protein telomeric repeat binding factor 1 (TRF1) was used. The influence on the stability of the telomeric complex of the presence of 8-oxoguanine (8oxoG) in the central telomeric triad (CTT) was estimated based on trajectories collected during 130 ns MD runs. The data obtained indicate that the system analyzed is highly sensitive to the presence of oxidative damage in the CTT of the B-DNA telomeric sequence. The most important changes were observed in the immediate vicinity of the 8-oxoguanine molecule. The significantly higher mobility of arginine 425 interacting directly with the oxidized guanine molecule has a large influence on the structural, dynamic and energetic properties of neighboring amino acids. Local changes observed for individual hydrogen bonded interactions localized in the major groove of B-DNA also have significant impact on the properties of hydrophobic clusters, which are the second type of force responsible for stability of the studied bio-system. All the changes reported in detail here unambiguously indicate a significant decrease in telomer binding affinity after oxidation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-013-1859-z) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2013-05-15 2013 /pmc/articles/PMC3713266/ /pubmed/23674370 http://dx.doi.org/10.1007/s00894-013-1859-z Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Paper
Czeleń, Przemysław
Cysewski, Piotr
Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations
title Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations
title_full Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations
title_fullStr Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations
title_full_unstemmed Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations
title_short Structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations
title_sort structural and energetic properties of canonical and oxidized telomeric complexes studied by molecular dynamics simulations
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713266/
https://www.ncbi.nlm.nih.gov/pubmed/23674370
http://dx.doi.org/10.1007/s00894-013-1859-z
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