How drugs interact and stabilize themselves in the vicinity of DNA? A computational quest

Deoxyribonucleic acid has been known cellular target for many anticancer agents from several decades. The interaction of drugs with nucleic acid is one of the important features in pharmacology and plays significant role to understand the mechanism of drug action and in designing of more efficient drugs with lesser side effects. In the current research work, diarylfurans which were claimed to possess antimicrobial tendencies were studied for their relative binding strengths and stable complex formation tendencies with DNA (PDB Id: 195D). Molecular docking calculations were performed to predict binding pocket of the drug in the vicinity of DNA and molecular dynamics (MD) were performed to study the interaction dynamics in support of predicted binding mode. Docking revealed that the binding site was AT-rich region, as preferred by minor groove binders. RMSD and RMSF analysis were done from the obtained from MD studies; the former study revealed that ligands remain bound to the preferred binding positions of the DNA without any considerable deviations in its minor groove; however the later revealed the topological structure of DNA remaining intact during the entire course of the simulation, inferring the stability of drug-DNA complexes. ADMET prediction studies were done in order to get an insight to the chemical perspectives of the drugs and their possible human bioassays. This study describes the properties and dynamics of DNA on the interaction with minor groove binders, taking the account of deformation upon binding which can play significant role in the discovery of new minor groove binder as a regulator of gene expression.