Conformation and flexibility of oligonucleotides containing O6-methylguanine: a molecular dynamics study

Abstract

A number of molecular dynamics simulations on oligonucleotides containing the alkylated base O⁶-methylguanine have been undertaken in order to determine the conformation and flexibility of such sequences. The conformations of a normal Watson–Crick and a G·T mismatch sequence, generated using a similar simulation procedure, are entirely consistent with the available experimental data. The sequence containing methyl-guanine base-paired with thymine (MeG·T) is iso-structural with the normal sequence irrespective of the conformation of the methyl group but with only two hydrogen bonds between the bases. In contrast, the conformation of the sequence containing methylguanine base-paired with cytosine (MeG·C) depends on the orientation of the methyl group and shows clear differences to the normal Watson–Crick hydrogen bonding. The methylated sequences have different flexibilities, with that containing methylguanine base-paired with cytosine being the more flexible. In summary, we find that the sequence containing MeG·T is closer to the normal sequence than that containing MeG·C and therefore is less likely to be recognised by repair enzymes.