Chapter 10 - Enzymatic recognition of radiation-produced oxidative DNA lesion. Molecular dynamics approach

Abstract

In the molecular dynamics (MD) approach, the structural and energy changes in DNA molecules are seen with respect to a proper recognition of the lesion by respective repair enzymes. Pyrimidine lesions (cytosinyl radical, thymine dimer, thymine glycol) and purine lesion (8-oxoguanine) were subjected to MD simulations for several hundreds of picoseconds using MD simulation code, Amber and its respective force field modified for each lesion. In most cases, the significant structural changes in DNA are observed: the breaking of the hydrogen bond network opening and bending the DNA double helix. These changes are related to the overall collapsing of the double helical structure around the lesion and are considered to facilitate the docking of repair enzymes into DNA and the formation of a DNA-enzyme complex. In addition to structural changes, the specific values of electrostatic interaction energy are detected at lesion sites, which are considered as a factor that enables repair enzymes to discriminate between lesion and undamaged DNA site. As a result of the MD simulations, in addition to the existing crystallographic and molecular biological techniques, they contribute to the studies of radiation carcinogenesis and DNA radiation damage repair by the dynamic description of the structural and chemical processes at the lesioned DNA molecules. Amber codes were installed and executed on three supercomputers.