Abstract
Binding of metal ions is an important factor governing the folding and dynamics of RNA. Shielding of charges in the polyanionic backbone allows RNA to adopt a diverse range of folded structures that give rise to their many functions within the cell. Some RNA sequences fold only in the presence of Mg(2+), which may be bound via direct interactions or occupy the more diffuse "ion atmosphere" around the RNA. To understand the driving forces for RNA folding, it is important to be able to fully characterize the distribution of metal ions around the RNA. In this work, a combined Grand Canonical Monte Carlo-Molecular Dynamics (GCMC-MD) method is applied to characterize Mg(2+) distributions around folded RNA structures. The GCMC-MD approach identifies known inner- and outer-shell Mg(2+) coordination, while also predicting new regions occupied by Mg(2+) that are not observed in crystal structures but that may be relevant in solution, including the case of the Mg(2+) riboswitch, for which alternate Mg(2+) binding sites may have implications for its function. This work represents a significant step forward in establishing a structural and thermodynamic description of RNA-Mg(2+) interactions and their role in RNA structure and function.