Conformational Deformations Triggered in B-DNA Dodecamer due to Major & Minor Groove Binders: Insights from QM & QM/MM Calculations

Deoxyribonucleic acid has become the target of interest in recent years for the number of anticancer and antimicrobial drugs. 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 effect drugs. The present study reports some antimicrobial classes of compounds and explores their molecular interaction with DNA using molecular modeling methods such as molecular docking, molecular dynamics simulation (MD) and quantum mechanics/molecular mechanics (QM/MM) studies. Molecular docking calculations were performed to predict binding pocket and Molecular Dynamics (MD) and quantum mechanics/ molecular mechanics (QM/MM) highly support the predicted binding mode. RMSD analysis reveals that ligands remain bound to the binding positions without any considerable deviation in the minor groove of DNA. This study shows that minor groove binders binds to the AT region of DNA via nonovalent interactions. QM/MM results are able to make direct comparison between DFT models in gas phase and in complete nucleic acid phase. It was also noticed that the noncovalent π-π interactions dominate other interactions during intercalation process. Understanding the binding of DNA-intercalators and role of noncovalent interactions allows for the cognitive design of new inhibitors. This study describes the properties and dynamics of DNA on the interaction with major & minor groove binders, taking the account of deformation upon binding which can play significant role in the discovery of new groove binders as a regulator of gene expression.