Competitive Binding of Mg and Na Ions to Nucleic Acids: From Helices to Tertiary Structures.

Nucleic acids generally reside in cellular aqueous solutions with mixed divalent/monovalent ions, and the competitive binding of divalent and monovalent ions is critical to the structures of nucleic acids because of their polyanionic nature. In this work, we first proposed a general and effective method for simulating a nucleic acid in mixed divalent/monovalent ion solutions with desired bulk ion concentrations via molecular dynamics (MD) simulations and investigated the competitive binding of Mg/Na ions to various nucleic acids by all-atom MD simulations. The extensive MD-based examinations show that single MD simulations conducted using the proposed method can yield desired bulk divalent/monovalent ion concentrations for various nucleic acids, including RNA tertiary structures. Our comprehensive analyses show that the global binding of Mg/Na to a nucleic acid is mainly dependent on its structure compactness, as well as Mg/Na concentrations, rather than the specific structure of the nucleic acid. Specifically, the relative global binding of Mg over Na is stronger for a nucleic acid with higher effective surface charge density and higher relative Mg/Na concentrations. Furthermore, the local binding of Mg/Na to a phosphate of a nucleic acid mainly depends on the local phosphate density in addition to Mg/Na concentrations.