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  4. Redox-Based Defect Detection in Packed DNA: Insights from Hybrid Quantum Mechanical/Molecular Mechanics Molecular Dynamics Simulations
 
research article

Redox-Based Defect Detection in Packed DNA: Insights from Hybrid Quantum Mechanical/Molecular Mechanics Molecular Dynamics Simulations

Kilic, Murat  
•
Diamantis, Polydefkis  
•
Johnson, Sophia K.  
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November 14, 2023
Journal of Chemical Theory and Computation

The impact of an 8-oxoguanine (8oxoG) defect on the redox properties of DNA within the nucleosome core particle (NCP) was investigated employing hybrid quantum mechanical/molecular mechanics (QM/MM) molecular dynamics simulations of native and 8oxoG-containing NCP systems with an explicit representation of a biologically relevant environment. Two distinct NCP positions with varying solvent accessibility were considered for 8oxoG insertion. In both cases, it is found that the presence of 8oxoG drastically decreases the redox free energy of oxidation by roughly 1 eV, which is very similar to what was recently reported for free native and 8oxoG-containing DNA. In contrast, the effect of 8oxoG on the reorganization free energy is even smaller for packed DNA (decrease of 0.13 and 0.01 eV for defect-free and defect-containing systems, respectively) compared to the one for free DNA (0.25 eV), consistent with the increased rigidity of the NCP as compared to free DNA. Furthermore, the presence of an 8oxoG defect does not yield any significant changes in the packed DNA structure. Such a conclusion favors the idea that in the case of chromatin, defect-induced changes in DNA redox chemistry can also be exploited to detect damaged bases via DNA-mediated hole transfer.

  • Details
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Type
research article
DOI
10.1021/acs.jctc.3c01013
Web of Science ID

WOS:001110611000001

Author(s)
Kilic, Murat  
Diamantis, Polydefkis  
Johnson, Sophia K.  
Toth, Oliver  
Rothlisberger, Ursula  
Date Issued

2023-11-14

Publisher

Amer Chemical Soc

Published in
Journal of Chemical Theory and Computation
Volume

19

Issue

22

Start page

8434

End page

8445

Subjects

Physical Sciences

•

Electron-Transfer Reactions

•

Oxidation-Reduction Reactions

•

Mediated Charge-Transport

•

Nucleosome Core Particle

•

Excision-Repair

•

Free-Energy

•

Crystal-Structure

•

Ionization

•

Damage

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8-Oxoguanine

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCBC  
FunderGrant Number

Partnership for Advanced Computing in Europe AISBL

2019204961

Swiss National Science Foundation (NSF)

200020_185092

CSCS

Available on Infoscience
February 20, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/204458
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