The energetics of small molecules binding with nucleic acids

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 goal of such analysis may be formulated in a form of answering two questions, viz. What physical factors and to what extent stabilize/destabilize ligand-NA complexes?' and What physical factor most highly correlates with the parameter of interest?' (e.g. the complexation constant or biological activity or else). Three groups of interactions were considered, viz. ligand-DNA intercalation, ligand-DNA minor groove binding and non-intercalative ligand binding to RNA aptamers. 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 drugs. (C) 2019 Elsevier Ltd.