Molecular dynamics simulation of DNA with a primary radiation damage

Molecular dynamics simulations have been conducted on a dodecamer of DNA d(CGCGAATTCGCG)₂ with a primary radiation damaged thymine in position 7. The damaged DNA has a local kink induced by the structural changes in the damaged thymine. The Watson-Crick base pairing in this region is disrupted. A global change in the structure of DNA is also seen in the form of a bend which contributes to shortening of the helix to the extent of 14%. The distortions are produced by the methyl group of the damaged thymine, which occupies a pseudoaxial position and produces steric interactions with the neighbouring residues. The possible biological consequences of such structural changes may be related to inhibition of polymerase action in the vicinity of the lesion. The results from the simulation indicate that within the short time explored in this study a spontaneous radical transfer from damaged thymine to sugar is unlikely.