Molecular dynamic simulation and DFT study on the Drug-DNA interaction; Crocetin as an anti-cancer and DNA nanostructure model.
In this research, the interaction of Crocetin as an anti-cancer drug and a Dickerson DNA has been investigated. 25 ns molecular dynamic simulations of Crocetin and DNA composed of 12 base pairs and a sequence of d(CGCGAATTCGCG)2were 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 PO⋯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. Average values of 0.3 au and zero for the electron densities of the H⋯O bonds for DNA and complex, obtained by Quantum theory of atoms in molecules (QTAIM), means that the origin of DNA instability after complexation may be related to the H-bond denaturation by Crocetin. Finally, the evaluation of the dispersion interactions using the dispersion functional, -148.76 kcal.mol-1, confirmed the importance of the dispersion interaction in drug-DNA complex.
a Faculty of Sciences, Department of Chemistry , Ferdowsi University of Mashhad , Mashhad , Iran.
Ebrahim
E
Azarhazin
a Faculty of Sciences, Department of Chemistry , Ferdowsi University of Mashhad , Mashhad , Iran.
Mohammad
http://orcid.org/0000-0002-3795-9982
M
Izadyar
a Faculty of Sciences, Department of Chemistry , Ferdowsi University of Mashhad , Mashhad , Iran.
Mohammad Reza
MR
Housaindokht
D020029:Base Pairing; D002338:Carotenoids / Q000737:chemistry* / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D006860:Hydrogen Bonding; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D049329:Nanostructures; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D013816:Thermodynamics; D014801:Vitamin A / Q000031:analogs & derivatives
D004273:DNA, Neoplasm; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids
Crocetin; DNA; Dickerson; binding energy; dispersion; hydrogen bond