Accessibility of deoxyribose hydrogens to hydroxyl radicals in nucleosomal and naked DNA in water: a molecular dynamics study with LAMMPS

Abstract Ionizing radiation induces DNA damage both directly and indirectly through hydroxyl radicals (·OH) generated by water radiolysis. The indirect action involves hydrogen abstraction from deoxyribose, leading to DNA damage such as base release and strand breaks. The probability of such events depends on the accessibility of specific hydrogen atoms to ·OH radicals. Previous computational studies have examined naked DNA fragments; however, the effect of nucleosomal organization has not been addressed. Here, we performed molecular dynamics (MD) simulations using LAMMPS (Large-scale Atomic Molecular Massively Parallel Simulator) to evaluate the accessibility of ·OH radicals to deoxyribose hydrogens in both 12-bp naked B-type DNA and nucleosomal DNA containing histone proteins. The accessibility to the hydrogens increased, following the order H1′ ≈ H2′ ≈ H3′ < H4′ < H5′, consistent with previous studies. Accessibility was approximately proportional to the solvent accessible surface area (SASA), supporting SASA as a practical predictor of accessibility even in base-dependent differences were observed. In nucleosomal DNA, accessibility of hydrogens facing the histone core was significantly reduced compared to solvent-facing hydrogens, despite comparable SASA values. This reduction suggests that histones physically hinder ·OH radical penetration. These findings highlight the importance of considering protein–DNA complexes when modeling indirect radiation effects.