The present review deals with energy analysis of ligand binding with nucleic acids in terms of the energy contribution from various physical factors making up the net Gibbs energy change of the complexation reaction measured in experiment. The general patterns in distribution of energy over various energy terms were discussed in terms of correlation with the ligand structure, binding affinity and biological activity. It was concluded, that the energy analysis, as a part of thermodynamic method of investigation of ligand-nucleic acid interactions, may provide an extension to scientific background of the strategy of rational design of DNA/RNA targeting drug
