Computational determination of radiation damage effects on DNA structure.

Molecular dynamics (MD) studies of several radiation originated lesions on the DNA molecules are presented. The pyrimidine lesions (cytosinyl radical, thymine dimer, thymine glycol) and purine lesion (8-oxoguanine) were subjected to the MD simulations for several hundred picoseconds using MD simulation code AMBER 5.0 (4.0). The simulations were performed for fully dissolved solute molecules in water. Significant structural changes in the DNA double helical structure were observed in all cases which may be categorized as: a) the breaking of hydrogen bonds network between complementary bases and resulted opening of the double helix (cytosinyl, radical, 8-oxoguanine); b) the sharp bending of the DNA helix centered at the lesion site (thymine dimer, thymine glycol); and c) the flippingout of adenine on the strand complementary to the lesion (8-oxoguanine). These changes related to the overall collapsing of the double helical structure around the lesion, are expected to facilitate the docking of the repair enzyme into the DNA in the formation of DNA-enzyme complex. The stable DNA-enzyme complex is a necessary condition for the onset of the enzymatic repair process. In addition to structural changes, specific values of electrostatic interaction energy were determined at several lesion sites (thymine dimer, thymine glycol and 8-oxoguanine). This lesion-specific electrostatic energy is a factor that enables repair enzyme to discriminate lesion from the native site during the scanning of the DNA surface. [ABSTRACT FROM AUTHOR]