Collect. Czech. Chem. Commun. 2008, 73, 161-174

Correlation Between the Thermodynamic Stability of DNA Duplexes and the Interaction and Solvation Energies of DNA Building Blocks

Jan Řezáč and Pavel Hobza*

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. and Center for Biomolecules and Complex Molecular Systems, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


The unwinding Gibbs energy (or duplex dissociation energy) is an important measure of the thermodynamic stability of DNA oligomers. This value can be measured experimentally or predicted by empirical models parametrised on experimental data. Our previously developed model based on accurate DFT-D calculations of interaction energies between nucleic acid bases corrected for solvation contribution. This work was successfully extended to cover variable lengths of oligomers. This model was further applied to oligomers containing inosine, an unnatural base. The results, however, are not satisfactory and it is clear that the model does not take into account all variables contributing to DNA stability. Inclusion of the backbone deformation energy did not improve the model. We also compared models based on DFT-D and forcefield calculations. Forcefield performs well in this application, because the systematic error in interaction energies is cancelled in the fitting procedure.

Keywords: DNA stability; Density functional theory; Stacking interactions; Solvation; DNA hybridization; DFT calculations; Thermodynamics.

References: 14 live references.