In the recent years, many researchers have been concentrated on the interaction analysis of small molecules with DNA. Recent advances in nanobiotechnology, molecular dynamic simulation and quantum chemistry calculations on drug DNA-complexes show that there are potentials for success in new drug discovery with DNA target. These simulations play an important role in rational drug design and description of the most probable state of binding of drugs to DNA. In this work, the interaction of Crocetin as an anticancer drug and a Dickerson DNA has been investigated. 25 ns molecular dynamic simulations of the Crocetin and DNA composed of twelve base pairs and a sequence of d(CGCGAATTCGCG)2 were done in water. Three definite parts of the B-DNA were considered in analyzing the best interactive site from the thermodynamic point of view. Binding energy analysis showed that van der Waals interaction is the most important part related to the reciprocal O and H atoms of the Crocetin and DNA. Stabilizing interactions, obtained by ΔG calculations, showed that maximum and minimum interactions are related to the S1 and S3 regions, respectively. This means that the most probable van der Waals interaction site of the Dickerson B-DNA and Crocetin is located in the minor groove of DNA. Two sharp peaks at 2.55 and 1.75 Å in radial distribution functions of the CO…..HO and NH…..OC parts are related to new hydrogen bonds between the Crocetin and DNA in the complex which can be considered as the driving force of the anti-cancer mechanism of the Crocetin.

Keywords