RNA Structural Complexity Dictates Its Ion Atmosphere

Electrostatic interactions mediated by surrounding ions critically influence RNA behavior, yet flexible RNAs remain underexplored. We performed molecular dynamics simulations to examine three RNAs across the structural continuum: unstructured poly uridylic tract (rU₃₀), a semiflexible cytosine-adenine-guanine (CAG) repeat, and a tightly folded pseudoknot. Despite similar net charges, rU₃₀ attracts a diffuse Mg²⁺ cloud extending beyond two hydration shells, while the CAG repeat and pseudoknot favor more compact outer-sphere Mg²⁺ binding. In contrast, Ca²⁺ consistently forms inner-sphere contacts across all three RNAs. Remarkably, the ion atmospheres around unstructured RNAs extend farther into solution than that of the folded RNAs, significantly broadening their electrostatic sphere of influence. Nonetheless, the ion exchange kinetics remain virtually unchanged, demonstrating a surprising decoupling between spatial distribution and dynamical turnover. Our findings reveal RNA structural flexibility as a powerful lever for tuning ionic screening, with important implications for biomolecular recognition, phase separation, and biophysical properties of RNA-rich condensates.