Molecular modeling of drug–DNA interactions: Virtual screening to structure-based design

Virtual ligand screening (VLS) and structure-based design are strategies that have been routinely used for the development of pharmaceuticals, particularly those targeting enzymes and other protein targets. In recent years, an increased understanding of the role played by nucleic acids in biological systems made DNA an alternative candidate for the development of new drugs. This review highlights some successful applications of molecular modeling in virtual ligand screening and structure-based design of organic and inorganic molecules that target non-canonical nucleic acid structures such as G-quadruplex and triplex DNA.

► We survey the recent literature on molecular modeling of drug–DNA interactions. ► The emerging use of computational technologies in lead discovery. ► In silico methods applied to triplex, G-quadruplex and minor groove binders. ► Virtual screening and structure-based design for the identification of novel scaffolds.