Figure 9.

Contrasting mechanisms by which Mg²⁺ and TMAO may stabilize the same RNA tertiary structure. The relative free energy (chemical potential) of folded (F) and unfolded (U) forms of a hypothetical RNA tertiary structure are diagrammed. In buffer, the U form of the RNA is represented as more stable than F (black boxes; the observed folding free energy, ΔG°_obs, is positive). Mg²⁺ interacts strongly (red arrows) with both U and F forms of the RNA, but preferentially stabilizes the native structure (red boxes; ΔG°_obs is now negative). TMAO interactions with both U and F forms are strongly unfavorable (blue arrows), but the U form is more strongly affected because of its more extensive exposure of phosphates to solvent. Therefore ΔG°_obs becomes negative (blue boxes).