Computational analysis of triplex formation of oligonucleotides:protonated and 5-methylated py-pu-py motif

Abstract

A triple helix composed of three dodecanucleotides, 5′-d(TC)6, 5′-(AG)6 and 3′-d(TC)6 with each containing a methylcytosine or a protonated-cytosine, was examined in terms of various interactions. Computational analysis of the stability of triplex formation was consistent with the experimental observations. The Hoogsteen base pairing interaction was increased through substitution of 5-methylcytosine for cytosine and/or protonation. The interaction between water molecules and DNA triplex was visualized in terms of the end-to-end distance change of each strand. The chain length was reduced by about 7.5 %–16.2 % due to the screening effect. In addition, as the screening effect increases, Hoogsteen base pairs appear to be stable in triplex formation. Our computational results also show that the effect of protonated- and methylated-cytosine on the stability of triplex formation was due to the change of the electrostatic interactions rather than the surface stacking interaction.