Understanding Cu⁺² binding with DNA: A molecular dynamics study comparing Cu²⁺ and Mg²⁺ binding to the Dickerson DNA

Cu²⁺ ions led DNA damage by reactive oxygen species (ROS) is widely known biological phenomena. The ionic radii of Cu²⁺ and Mg²⁺ being similar, the binding of Cu²⁺ ions to DNA is expected to be similar to that of the Mg²⁺ ions. However, little is known how Cu²⁺ ions bind in different parts (phosphate, major and minor grooves) of a double-strand (ds) DNA, especially at atomic level. In the present study, we employ molecular dynamic (MD) simulations to investigate the binding of Cu²⁺ ions with the Dickerson DNA, a B-type dodecamer double stranded (ds) DNA. The binding characteristics of Cu²⁺ and Mg²⁺ ions with this dsDNA are compared to get an insight into the differences and similarities in binding behavior of both ions. Unlike Mg²⁺ ions, the first hydration shell of Cu²⁺ is found to be labile, thus it shows both direct and indirect binding with the dsDNA, i.e., binding through displacement of water from the hydration shell or through the hydration shell. Though the binding propensity of Cu²⁺ ions with dsDNA is observed relatively stronger, the binding order to phosphates, major groove, and minor groove is found qualitatively similar (phosphates > major groove > minor groove) for both ions. The study gives a deep understanding of Cu²⁺ binding to DNA, which could be helpful in rationalizing the Cu²⁺ led ROS-mediated DNA damage.