Predicting electrostatic forces in RNA folding

Metal ion-mediated electrostatic interactions are critical to RNA folding. Although considerable progress has been made in mechanistic studies, the problem of accurate predictions for the ion effects in RNA folding remains unsolved, mainly due to the complexity of several potentially important issues such as ion correlation and dehydration effects. In this chapter, after giving a brief overview of the experimental findings and theoretical approaches, we focus on a recently developed new model, the tightly bound ion (TBI) model, for ion electrostatics in RNA folding. The model is unique because it can treat ion correlation and fluctuation effects for realistic RNA 3D structures. For monovalent ion (such as Na(+)) solutions, where ion correlation is weak, TBI and the Poisson-Boltzmann (PB) theory give the same results and the results agree with the experimental data. For multivalent ion (such as Mg(2+)) solutions, where ion correlation can be strong, however, TBI gives much improved predictions than the PB. Moreover, the model suggests an ion correlation-induced mechanism for the unusual efficiency of Mg(2+) ions in the stabilization of RNA tertiary folds. In this chapter, after introducing the theoretical framework of the TBI model, we will describe how to apply the model to predict ion-binding properties and ion-dependent folding stabilities.