Large scale MD simulation of 8-oxoguanine and AP site multiple lesioned DNA molecule combined with biomolecular visualization software

Fujimoto, Haruhiro; Pinák, Miroslav; Nemoto, Toshiyuki; Sakamoto, Kiyotaka; Yamada, Katsushi; Hoshi, Yosuke; Kume, Etsuo

doi:10.1016/j.theochem.2003.12.053

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…Besides, short 1ns molecular dynamics simulations were performed for elucidation of the effect of guanine lesion presence in B-DNA [19]. Much larger MD simulation were carried out by Fujimoto et al combined with biomolecular visualization software [20]. However, most of theoretical studies on 8-oxoguanine in B-DNA are related to explanation [21,22] f activities of human oxoguanine glycosylase (hOGG1) [23][24][25][26] and TRF1 binding was analyzed with much lower intensity [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Structural and energetic consequences of oxidation of d(ApGpGpGpTpT) telomere repeat unit in complex with TRF1 protein

Cysewski

Czeleń

2010

J Mol Model

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International audienceThe configuration hyperspace of canonical and oxidized 14-mers of B-DNA comprising telomere repeat units d(ApGpGpGpTpT) was sampled over 40 ns molecular dynamic (MD) simulations. The energetic and structural consequences of TRF1 binding to telomere B-DNA were compared with non-complexed systems. Energetic properties of analyzed pairs, di- and tri-nucleotide steps occurring in central telomere repeat unit were estimated by means of advanced quantum chemistry computations including not only BSSE corrections, electron correlation contributions but also non-negligible many-body terms. These data along with bases pair and base step parameters distributions allow for quantization of consequences of oxidation and/or TRF1 binding to telomere repeat units. Occurrence of 8-oxoguanine in central telomeric triad (CTT) is the source of high stiffness if compared to non-modified oligomer. The origin of this property comes from significantly alteration of intermolecular interactions introduced by 8-oxoguanine. The increased stability observed for base-base interactions are accumulated and characterizes also di- and tri-nucleotides. The observed changes in the intermolecular interactions originate from structural alterations imposed by TRF1 binding to canonical and oxidized telomere B-DNA. First and most direct consequence of TRF1 binding to oxidized telomere repeat unit is alteration of - correlations if compared to canonical system. This in turn leads to large differences in purine-purine overlapping in oxidized structures. Thus, oxidized telomere B-DNA double strands are sensitive to interactions with protein ligands and numerous structural and energetic changes are imposed on base pairs forming CTT

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Section: Introductionmentioning

confidence: 99%

Structural and energetic consequences of oxidation of d(ApGpGpGpTpT) telomere repeat unit in complex with TRF1 protein

Cysewski

Czeleń

2010

J Mol Model

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“…These changes were compared with those of ordinary native (nonlesioned) DNA molecules. One of the six DNA containing clustered damage sites has been recently examined and found to have specific structural conformations 25. Because sequences of each of the six DNA molecules were designed to correspond to those that were used experimentally in previous reports,6, 16, 18, 19 results obtained from simulations presented here are compared with those reported experimentally to gain insights into the MD changes resulting when a second lesion is in close proximity to another lesion in a clustered DNA damage site.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulation of clustered DNA damage sites containing 8‐oxoguanine and abasic site

et al. 2005

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Clustered DNA damage sites induced by ionizing radiation have been suggested to have serious consequences to organisms, such as cancer, due to their reduced probability to be repaired by the enzymatic repair machinery of the cell. Although experimental results have revealed that clustered DNA damage sites effectively retard the efficient function of repair enzymes, it remains unclear as to what particular factors influence this retardation. In this study, approaches based on molecular dynamics (MD) simulation have been applied to examine conformational changes and energetic properties of DNA molecules containing clustered damage sites consisting of two lesioned sites, namely 7,8-dihydro-8-oxoguanine (8-oxoG) and apurinic/apyrimidinic (AP) site, located within a few base pairs of each other. After 1 ns of MD simulation, one of the six DNA molecules containing a clustered damage site develops specific characteristic features: sharp bending at the lesioned site and weakening or complete loss of electrostatic interaction energy between 8-oxoG and bases located on the complementary strand. From these results it is suggested that these changes would make it difficult for the repair enzyme to bind to the lesions within the clustered damage site and thereby result in a reduction of its repair capacity.

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Large scale MD simulation of 8-oxoguanine and AP site multiple lesioned DNA molecule combined with biomolecular visualization software

Cited by 2 publications

References 14 publications

Structural and energetic consequences of oxidation of d(ApGpGpGpTpT) telomere repeat unit in complex with TRF1 protein

Structural and energetic consequences of oxidation of d(ApGpGpGpTpT) telomere repeat unit in complex with TRF1 protein

Molecular dynamics simulation of clustered DNA damage sites containing 8‐oxoguanine and abasic site

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