The results obtained through hydrogen bonding analysis suggested that complex-1 had both donor and acceptor clouded regions essential for the formation of hydrogen bonds but due to presence of bulky groups greater interactions could not be achieved. However, complex-2 had greater extent of donor clouded regions but due to presence of non-bulky substituents, hydrogen bonding was preferred. This analysis also represented the DNA bases involved in the hydrogen bond formations. Molecular dynamics simulation shows the time evolution of the stability of ligands in the vicinity of DNA. Radius of gyration, hydrogen bonding, RMSD and RMSF analysis were done from the trajectories obtained via MD studies; all these results favor the stable complex formation for lig-2 with 1BNA. Radius of gyration & RMSD values reveal that ligands remain bound to the preferred binding positions of the DNA without any considerable deviations; whereas the hydrogen bonding data reveals that complex-2 has greater number of hydrogen interactions, as predicted by docking calculations. RMSF analysis revealed that the topological structure of DNA remains intact during the entire course of the simulation, inferring the stability of drug-DNA complexes. QM/MM calculations were then carried out for better understanding of the results obtained through MD simulations. The results obtained suggest that since binding energies for lig-2 is less than lig-1, so complex-2 has the most stable complex. Because lig-2 did not offer any steric hindrances during the DFT studies and hence the repulsions between their nearest bonded atoms, between the angles and between corresponding dihedrals was minimized and the complex-2 attained an energy state having least bonded repulsions and therefore maximum stability was achieved and that state would correspond to minimum energy. Molecular docking predicted the binding pockets and MD simulation results highly support the predicted binding site. RMSD and RMSF analysis also indicate that none of the compounds detached from the system throughout the simulation. Advanced computational techniques such as, QM/MM calculations also predicted the similar results as obtained via molecular docking and molecular dynamics simulation, owing to incorporation of DFT. The results obtained through computational calculations not only predicted the conformational stability of the DNA with the ligands but also gave a firm affirmation regarding the time dependence of the interaction and stability of drug-DNA complexes. The extension of such studies involving computational techniques is not only limited to drug design and molecular modelling but also to drug metabolism.