A repulsive field: advances in the electrostatics of the ion atmosphere

The large electrostatic repulsion arising from the negatively chargedbackboneofRNAmoleculespresents alarge barrierto folding. Solution counterions assist in the folding process by screening this electrostatic repulsion. While early research interpreted the effect of these counterions in terms of an empirical ligand-binding model, theories based on physical models have supplanted them and revised our view of the roles that ions play in folding. Instead of specific ion-binding sites, most ions in solution interact inside an ‘ion atmosphere’ — a fluctuating cloud of nonspecifically associated ions surrounding any charged molecule. Recent advances in experiments have begun the task of characterizing the ion atmosphere, yielding valuable data that have revealed deficiencies in Poisson–Boltzmann theory, the most widely used theoryoftheionatmosphere. Thecontinued development of experiments will help guide the development of improved theories, with the ultimate goal of understanding RNA folding and function and nucleic acid/protein interactions from a quantitative perspective.