Divalent Ion-Mediated DNA-DNA Interactions: A Comparative Study of Triplex and Duplex.

Ion-mediated interaction between DNAs is essential for DNA condensation, and it is generally believed that monovalent and nonspecifically binding divalent cations cannot induce the aggregation of double-stranded (ds) DNAs. Interestingly, recent experiments found that alkaline earth metal ions such as Mg can induce the aggregation of triple-stranded (ts) DNAs, although there is still a lack of deep understanding of the surprising findings at the microscopic level. In this work, we employed all-atom dynamic simulations to directly calculate the potentials of mean force (PMFs) between tsDNAs, between dsDNAs, and between tsDNA and dsDNA in Mg solutions. Our calculations show that the PMF between tsDNAs is apparently attractive and becomes more strongly attractive at higher [Mg], although the PMF between dsDNAs cannot become apparently attractive even at high [Mg]. Our analyses show that Mg internally binds into grooves and externally binds to phosphate groups for both tsDNA and dsDNA, whereas the external binding of Mg is much stronger for tsDNA. Such stronger external binding of Mg for tsDNA favors more apparent ion-bridging between helices than for dsDNA. Furthermore, our analyses illustrate that bridging ions, as a special part of external binding ions, are tightly and positively coupled to ion-mediated attraction between DNAs.