Folded ribonucleic acids (RNAs) are increasingly recognized as key components in a diverse spectrum of biological functions. In addition, the wide distribution of these sequences in bacterial genomes suggests folded RNAs could represent an exciting new class of antimicrobial drug targets. The development of RNA binding drugs requires a detailed understanding of the energetic contributions to binding. However, the contribution of electrostatics, hydrogen bonding, sterics and entropic effects to these binding events is still poorly understood.
We investigate small molecule binding in a class of structured RNAs called riboswitches. We combine the tools of synthetic organic chemistry, biophysical spectroscopy, and RNA biochemistry to establish structure function relationships for the binding of small molecules to the preQ1 riboswitch.