In this research, the interaction of safranal (2,6,6-trimethylcyclohexa-1,3-dien-1-carboxaldehyde) as an anti-cancer drug and a Dickerson B-DNA by a combination of the quantum mechanics and molecular dynamic (MD) simulations was studied. MD simulations were executed for 35 ns in water. Binding energy analysis in three definite parts of the B-DNA and comparison between different contributions of the binding energy shows that van der Waals energy part of the interaction is impressive among the standard molecular mechanic energy terms. On the basis of Gibbs energies, it is confirmed that the most important interactions in the safranal complex are related to the A-T and C-G rich regions in agreement with the experimental data. Quantum theory of atoms in molecules and natural bond orbital analyses were applied. A diminution in the electronic chemical potential of the safranal- DNA complex in comparison with the isolated DNA, 0.026 and 0.022 au for S1 region, 0.012 and 0.017 au for S2 region was obtained in the gas phase and water, respectively, which increases the complex stability. An enhancement in the electrophilicity character, during the complexation process, shows the electron charge flux between the safranal and DNA, especially in water. The strengths of the CH…O bonds at the center of DNA-safranal interaction were also evaluated. An average value of 0.06 au for the electron density of the bond critical point of the H….O in the complex confirms the H-bond formation during the complexation.

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