Evaluation of DNA- Targeted Anticancer Interaction by Molecular Dynamic Simulation; Ethyl Butyryl TriphenylPhosphonium Chloride

In recent years, many researches have been focused on interaction of small molecules withDNA. DNA is generally the primary intracellular target of anticancer drugs, so the interactionbetween small molecules and DNA can cause DNA damage in cancer cells, inhibiting thegrowth of cancer cells and resulting in cells death. Generally, DNA is the typical target ofmany anti-cancer drugs. Although the studies showed many new cationic phosphonium saltsa remarkable anti-cancer activity, but the mechanism in the anti-cancer process is not clear.In this research, the interaction of ethyl butyryl triphenyl phosphonium chloride as ananticancer drug with a DNA which composed of twelve base pairs (Dickerson dodecamer)has been investigated. Molecular dynamic (MD) simulation of the DNA and drug in water wasdone for 3 ns. All MD simulations have been performed using the Amber package within theAmber force field of AMBERff99SB and general amber force fields (GAFF) for DNA and drug,respectively. Two definite regions on the B-DNA (minor (S1) and major (S2) grooves) havebeen considered to analyze the best interaction site. Gibbs free energy and entropy changeshave been calculated at this regions. The stabilizing interactions, obtained by Î Gcalculations, showed that maximum interaction is related to the S1 region which means ananticancer nature for this drug. The anti- cancer effect of this drug is correlated with theinteraction at the minor groove by van der Walls and hydrogen binding.

Keywords:

MD Simulation , Drug-DNA Interaction , Anticancer , Dickerson , Gibbs Free Energy