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

12 September 2023, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


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, 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 eV and 0.01 eV for defect-free and defect-containing systems respectively) compared to the one of 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 packed DNA structure. Such a conclusion favors the idea that also in the case of chromatin, defect-induced changes in DNA redox chemistry can be exploited to detect damaged bases via DNA mediated hole transfer.


Nucleosome Core Particle
Oxidative Damage

Supplementary weblinks


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