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 Mg concentrations. The DCC model includes explicit interaction of the ligand and adjacent chelated Mg 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-Mg to induce stem-I and stem-II closure where the minor groove between these stems is akin to breathing. Mg 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 Mg for the tertiary structure of RNA, the study warns about the plausible detrimental effect of specific Mg-phosphate interactions on the RNA-PK structure beyond a certain concentration of Mg.