Thymine-methyl/π interaction implicated in the sequence-dependent deformability of DNA

The crystal structures of deoxy-oligonucleotides were retrieved from the Nucleic Acid Database and analyzed with the use of our program CHPI. The structure of 5′-ApTpApT-3′ has been shown to be stabilized by the 5-methyl group in the thymidine moiety that favorably interacts with the adenine π-ring preceding it. H2′ of the deoxyribose in adenine also interacts with the thymine ring next to it. Since a 5′-ApT-3′ sequence is accompanied by another 5′-ApT-3′ in the complementary strand, the interaction is duplicated, thus forming a ‘twin A/T-Me interaction’. Coordinates of oligonucleotides with A-T rich sequences were retrieved and analyzed. In almost every case, the thymidine 5-methyl group favorably interacts with an adenine ring in the same strand. The structure of duplexes incorporating A-tracts was also analyzed. The 5-methyl group in the thymidine moiety has been found to interact favorably with the base π-ring before it. Since an A-tract is lined with an oligo-T sequence in the complementary strand, a successive N/T-Me stacking may contribute in making the A-tracts robust and straight. The possible involvement of the N/T-Me and the twin A/T-Me motif in the deformability of DNA has been suggested. The role of methyl groups in modified DNA has been discussed on a similar basis.