Nonspecific binding, which is closely related to electrostatic and stacking interactions , cause many side effects when tested clinically . Despite recent efforts on designing drug-like small molecules while overcoming non-specific binding to RNAs , selectivity is still a challenge. Design of small molecules, which can stabilize transient RNA conformations, can improve selectivity and provide a solution to nonspecific binding. Indeed, many regulatory RNAs can form low populated conformations, which display alternate base pairings especially in dynamic RNA loop motifs such as internal and bulge loops . Minor populations have been observed in riboswitches and HIV-1 transactivation response element (TAR) that has important implications in recognition, which provide selectivity upon ligand binding.