Predicting Ion Binding Properties for RNA Tertiary Structures

Recent experiments pointed to the potential importance of ion correlation for multivalent ions such as Mg²⁺ ions in RNA folding. In this study, we develop an all-atom model to predict the ion electrostatics in RNA folding. The model can treat ion correlation effects explicitly by considering an ensemble of discrete ion distributions. In contrast to the previous coarse-grained models that can treat ion correlation, this new model is based on all-atom nucleic acid structures. Thus, unlike the previous coarse-grained models, this new model allows us to treat complex tertiary structures such as HIV-1 DIS type RNA kissing complexes. Theory-experiment comparisons for a variety of tertiary structures indicate that the model gives improved predictions over the Poisson-Boltzmann theory, which underestimates the Mg²⁺ binding in the competition with Na⁺. Further systematic theory-experiment comparisons for a series of tertiary structures lead to a set of analytical formulas for Mg²⁺/Na⁺ ion-binding to various RNA and DNA structures over a wide range of Mg²⁺ and Na⁺ concentrations.