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

• DOI: 10.1021/acs.jctc.3c01013
• Publication Date: 2023-11-14T21:48:29Z
• Authors: Murat Kılıç; Polydefkis Diamantis; Sophia K. Johnson; Oliver Toth; Ursula Rothlisberger
• Keywords: Molecular mechanics

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