Computational study of the pKa values of a modified G C base pair in duplex DNA

摘要

During the demethylation of 5-methyl cytosine residues in duplex DNAs,formyl or carboxyl cytosines are produced and these modified cytosines are preferentially recognized and excised by the thymine DNA glycosylase(TDG).It has been suggested that the TDG detects a soft spot created by weakening of the hydrogen bond of a GC base pair(bp).Such bp destabi-lization is ascribed to the presence of electron-withdrawing 5-formyl or 5-carboxyl group in the modified cytosine.Previously,this bp weakening was linked to reduced pKa values of nucleoside molecules.However,the pKa values of nucleosides can deviate from those of duplex DNAs.Thus,to improve agreement with experiments,the corresponding pKa values for DNA environments are needed.In this computational study,we report two pKa values of the N3-and the C5-carboxyl sites in the 5-carboxyl cytosine residue in a duplex DNA that enable more reasonable interpretations of previous experimental data.