Molecular Dynamics Simulation of Crocin and Dimethylcrocetin Interactions with DNA

In this work, the interactions of the crocin and dimethylcrocetin (DMC) as anti-cancer drugs with the Dickerson DNA model was investigated. Molecular dynamic simulations of Crocin, DMC and DNA composed of twelve base pairs and a sequence of the d(CGCGAATTCGCG)2 were executed for 25 ns in water. Binding energy analysis for each of the complexes in three definite parts of BDNA showed that Van der Waals interactions have a dominant contribution in energy values. Crocin-DNA interactions are greater than those of DMC-DNA, due to a longer Π-conjugation. The most probable interactions were detected by Gibbs energy analysis, indicating that the stabilizing interactions of the DNA with crocin and DMC are located in the major and minor grooves of the DNA, respectively. In the case of DMC, the binding energy of the A-T rich sequence is more than that of G-C which is different from crocin. Radial distribution function analysis showed that two sharp peaks of the CO…NH and HO…OC parts, during the complex formation at 2.16 Å and 2.28 Å, could be assinged to the new hydrogen bond formation between DMC and crocin with DNA, respectively. Also, non-classical H-bonds were investigated by considering the CH group of the drug and OC/NC groups of DNA that play an important role in the stability of the DNA in the corresponding complex.