Dynamics has been shown to be a key determinant in a variety of RNA functions and local dynamics could affect ligand binding capacity broadly. If the structure of a target RNA is too dynamic, ligand binding potential could be diminished. That is, a defined small molecule binding pocket may not be present, or the affinity of an ill-defined pock could be low due to energetic and entropic penalties associated with locking out multiple conformations. Previous studies have provided some insight into RNA structural dynamics such as smaller loops are not typically as conformationally dynamic as their larger counterparts and U-rich motifs can have dynamic character. We were therefore interested in if the SMIRNAs studied herein had a preference for dynamic or structurally well-defined loops. Fortuitously, a set of structurally related small molecules had overlap in the RNAs that they preferred to bind and those that they discriminated against. We studied the structural dynamics of these loops by nuclear magnetic resonance (NMR) spectroscopy. As shown in Figure , RNAs that bind small molecules have defined structure, as evidenced by the presence of all possible imino proton peaks.