Understanding Cu binding with DNA: A molecular dynamics study comparing Cu and Mg binding to the Dickerson DNA.

Cu ions led DNA damage by reactive oxygen species (ROS) is widely known biological phenomena. The ionic radii of Cu and Mg being similar, the binding of Cu ions to DNA is expected to be similar to that of the Mg ions. However, little is known how Cu 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 Cu ions with the Dickerson DNA, a B-type dodecamer double stranded (ds) DNA. The binding characteristics of Cu and Mg ions with this dsDNA are compared to get an insight into the differences and similarities in binding behavior of both ions. Unlike Mg ions, the first hydration shell of Cu 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 Cu 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 Cu binding to DNA, which could be helpful in rationalizing the Cu led ROS-mediated DNA damage.