Dynamic effects of the spine of hydrated magnesium on viral RNA pseudoknot structure

In the cellular environment, a viral RNA Pseudoknot (PK) structure is responsive to its prevailing ion atmosphere created by a mixture of monovalent and divalent cations. We investigate the influence of such a mixed-salt environment on RNA-PK structure at an atomic resolution through three sets of 1.5 μs explicit solvent molecular dynamics (MD) simulations and also by building a dynamic counterion-condensation (DCC) model at varying divalent Mg²⁺ concentrations. The DCC model includes explicit interaction of the ligand and adjacent chelated Mg²⁺ by extending the recently developed generalized Manning condensation model. Its implementation within an all-atom structure-based molecular dynamics framework bolsters its opportunity to explore large-length scale and long-timescale phenomena associated with complex RNA systems immersed in its dynamic ion environment. In the present case of RNA-PK, both explicit MD and DCC simulations reveal a spine of hydrated-Mg²⁺ to induce stem-I and stem-II closure where the minor groove between these stems is akin to breathing. Mg²⁺ mediated minor-groove narrowing is coupled with local base-flipping dynamics of a base triple and quadruple, changing the stem structure of such RNA. Contrary to the conversational view of the indispensable need for Mg²⁺ for the tertiary structure of RNA, the study warns about the plausible detrimental effect of specific Mg²⁺-phosphate interactions on the RNA-PK structure beyond a certain concentration of Mg²⁺.