Metal ions play an important role in the structure and function of nucleic acids, including DNA replication and efficient DNA packing. An increased concentration of positively charged ions near double strand DNA (dsDNA) neutralizes the excess negative charge of the phosphate backbone. Divalent metal ions are more efficient at neutralizing the phosphate backbone charge and displace monovalent ions near dsDNA. These DNA-ion interactions are exploited in the development of DNA-based nanoscale devices. In these applications, divalent metal ions are used to stabilize the DNA duplex structure and to quench spectroscopy signals of chromophore-tagged DNA. The type of divalent ion affects the structure and dynamic behavior of dsDNA. Classical molecular dynamics simulations provide statistically relevant sampling of DNA-ion structures that can be analyzed to identify preferred binding sites and motifs. Previous studies have examined the interaction of biologically relevant metal ions such as Ca2+ and Mg2+ with DNA, but few studies have studied the interactions of transition metal ions with DNA due, in part, to a lack of reliable force field parameters for transition metals ions. Using Lennard-Jones parameters optimized to reproduce both experimental hydration free energies and coordination numbers of divalent metal ions, we identify preferential binding sites of Ni2+, Co2+, Mg2+, Ca2+, Sr2+, and Ba2+ to dsDNA. We quantitatively compare binding to the phosphate backbone, major groove, and minor groove, with an emphasis on verifying previous reports that transition metal ions preferentially bind to the guanine N7 site in the major groove of dsDNA. Clear trends in direct and indirect binding are observed for the transition metal and alkaline earth metal ions studied.

Binding of transition and alkaline earth metal ions with a DNA duplex from classical molecular dynamics simulations

2019 Spring National Meeting

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