Abstract
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(2+)/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(2+)/Na(+) to a nucleic acid is mainly dependent on its structure compactness, as well as Mg(2+)/Na(+) concentrations, rather than the specific structure of the nucleic acid. Specifically, the relative global binding of Mg(2+) over Na(+) is stronger for a nucleic acid with higher effective surface charge density and higher relative Mg(2+)/Na(+) concentrations. Furthermore, the local binding of Mg(2+)/Na(+) to a phosphate of a nucleic acid mainly depends on the local phosphate density in addition to Mg(2+)/Na(+) concentrations.