DNA-cation interactions: quo vadis?

The interactions between double helical DNA and cations, specifically mono- and divalent metal ions, have recently received increased attention. Molecular dynamics simulations, solution NMR, and X-ray crystallography have all shed light on the coordination of ions in the major and minor grooves of DNA. Metal ion interactions may play key roles in the control of DNA conformation and topology, but despite progress in locating the ions and determining their precise binding modes, it remains difficult to figure out just how important ions really are. What have we learned and what remains to be done?