Design de Medicamentos: Acesso Aberto
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Interaction, Dynamics and Stability Analysis of Some Minor Groove Binders with B-DNA Dodecamer 5' (CGCAAATTTGCG)-3'

Anwesh Pandey, Anurag Upadhyaya, Suresh Kumar, Anil Kumar Yadav

Deoxyribonucleic Acid (DNA) has been a known cellular target for many antibacterial and anticancer agents due to its gene expression tendencies. The interaction of drugs with nucleic acid is one of the important features in pharmacology and plays a significant role in understanding the mechanism of drug action and in designing of more efficient drugs with minimal side effects. Furans have been known since long and are often claimed to have possessed various medicinal and therapeutic tendencies. In the current research work, two class of molecules viz, 2,4-bis(4-amidinophenyl)furans and reversed diamidino 2,5-diarylfurans, were computationally studied for their relative binding strengths and stable complex formation tendencies with DNA (PDB Id: 4AH0). Molecular docking was performed to predict binding pocket of the drug in the vicinity of DNA and molecular dynamics was performed to study the interaction dynamics in support of the 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. This study describes the properties and dynamics of DNA on the interaction with furan derivatives, 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. In this study, we also performed Natural Bond Orbital (NBO) Analysis using Gaussian 09 program package for the calculation of intra and intermolecular orbital bonding and interaction in the optimized electronic chemical structure, particularly charge transfer and stabilization gain energy.