DNA/TNA mesoscopic modeling of melting temperatures suggests weaker hydrogen bonding of CG than in DNA/RNA

[Display omitted] •Mesoscopic parameters of DNA/TNA hybrids were obtained from melting temperatures and compared to DNA/RNA.•Base pairs involving AT in DNA/RNA were found to have similar hydrogen bonding strength as for DNA/RNA.•For CG, base pairing strength is significantly reduced, but this is compensated for by a stronger stacking interaction.•Opening profiles for DNA/TNA are mostly flatted out with little difference between AT and CG regions. TNA/DNA hybrids share several similarities to RNA/DNA, such as the tendency to form A-type helices and a strong dependency of their thermodynamic properties on purine/pyrimidine ratio. However, unlike RNA/DNA, not much is known about the base-pair properties of TNA. Here, we use a mesoscopic analysis of measured melting temperatures to obtain an estimate of hydrogen bonds and stacking interactions. Our results reveal that the AT base pairs in TNA/DNA have nearly identical hydrogen bond strengths than their counterparts in RNA/DNA, but surprisingly CG turned out to be much weaker despite similar stability.