Oxidative Defect Detection Within Free and Packed DNA Systems: A Quantum Mechanical/Molecular Mechanics (QM/ MM) Approach

• DOI: 10.2533/chimia.2024.243
• Publication Date: 2024-04-24T07:05:05Z
• Authors: Sophia Johnson; Ursula Rothlisberger
• Keywords: DNA Repair; Dna; DNA; Molecular dynamics; Molecular Dynamics Simulation; Molecular Dynamics; QM/MM; 01 natural sciences; Chromatin; 0104 chemical sciences; Oxidative Damage; Chemistry; Oxidative damage; Quantum Theory; QD1-999; Oxidation-Reduction; Qm/Mm; DNA Damage

Base excision repair enzymes (BERs) detect and repair oxidative DNA damage with efficacy despite the small size of the defects and their often only minor structural impact. A charge transfer (CT) model for rapid scanning of DNA stretches has been evoked to explain the high detection rate in the face of numerous, small lesions. The viability of CT DNA defect detection is explored via hybrid QM/MM computational studies that leverage the accuracy of quantum mechanics (QM) for a region of interest and the descriptive power of molecularmechanics (MM) for the remainder of the system. We find that the presence of an oxidative lesion lowers theredox free energy of oxidation by approximately 1.0 eV regardless of DNA compaction (free DNA versus packed DNA in nucleosome core particles) and damage location indicating the high feasibility of a CT-based process for defect detection in DNA.