Exploring the electrostatic energy landscape for tetraloop–receptor docking

Abstract

It has long been appreciated that Mg²⁺ is essential for the stabilization of RNA tertiary structure. However, the problem of quantitative prediction for the ion effect in tertiary structure folding remains. By using the virtual bond RNA folding model (Vfold) to generate RNA conformations and the newly improved tightly bound ion model (TBI) to treat ion–RNA interactions, we investigate Mg²⁺-facilitated tetraloop–receptor docking. For the specific construct of the tetraloop–receptor system, the theoretical analysis shows that the Mg²⁺-induced stabilizing force for the docked state is predominantly entropic and the major contribution comes from the entropy of the diffusive ions. Furthermore, our results show that Mg²⁺ ions promote tetraloop–receptor docking mainly through the entropy of the diffusive ions. The theoretical prediction agrees with experimental analysis. The method developed in this paper, which combines the theory for the (Mg²⁺) ion effects in RNA folding and RNA conformational sampling, may provide a useful framework for studying the ion effect in the folding of more complex RNA structures.