PNNL

Abstract

hanges of electrostatic potential (EP) around the DNA molecule resulting from chemical modifications of nucleotides may play a role in enzymatic recognition of damaged sites. Effects of chemical modifications of nucleotides on the structure of DNA have been characterized through large scale density functional theory computations. Quantum mechanical structural optimizations of DNA fragments with three pairs of nucleotoides and accompanying counteractions were performed with a B3LYP exchange-correlation functional and 6-31G** basis sets. The “intact” DNA fragment contained guanine in the middle layer, while the “damaged” fragment had the guanine replaced with 8-oxo-guanine. The electrostatic potential around these DNA fragments was projected on a surface around the double helix. The 2D maps of EP of intact and damaged DNA fragments were analyzed to identify these modifications of EP that result from the occurrence of 8-oxo-guanine. It was found that distortions of the phosphate groups and displacements of the accompanying countercations are clearly reflected in the EP maps.