MOLECULAR-DYNAMICS SIMULATION OF DNA WITH A PRIMARY RADIATION-DAMAGE

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