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Abstract
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.
Supplementary weblinks
Title
Supplementary Information for Redox-Based Defect Detection in Packed DNA: Insights from Hybrid Quantum Mechanical/Molecular Mechanics Molecular Dynamics Simulations
Description
Zenodo repository for the supplementary document associated with this work contains (for all systems) including: Figures with the vertical energy gap distributions, Tables with the RMSFs of DNA residues belonging in the QM region of all systems, Tables with the identified DNA-protein close contacts, Table of average hydrogen-bonding interactions with the defect regions and solvent molecules, all 41 structural parameter distribution plots, select section-by-section structural parameter plots, RMSF plots of base flexibility for four DNA sections, and DNA-water radial distribution functions for the phosphorous atoms of the DNA backbone near the quantum region and oxygen atoms in water.
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Supplementary Information for Redox-Based Defect Detection in Packed DNA: Insights from Hybrid Quantum Mechanical/Molecular Mechanics Molecular Dynamics Simulations
Description
Github repository for the supplementary document associated with this work contains (for all systems) including: Figures with the vertical energy gap distributions, Tables with the RMSFs of DNA residues belonging in the QM region of all systems, Tables with the identified DNA-protein close contacts, Table of average hydrogen-bonding interactions with the defect regions and solvent molecules, all 41 structural parameter distribution plots, select section-by-section structural parameter plots, RMSF plots of base flexibility for four DNA sections, and DNA-water radial distribution functions for the phosphorous atoms of the DNA backbone near the quantum region and oxygen atoms in water.
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