In the past year, efforts have been made in collaboration with Dr. J. Schneekloth at NCI to characterize, in structural terms, the modes of RNA interaction of a number of small molecule compounds that have been found to bind with high affinity to serveral bacterial riboswitches. We have also collaborated with Dr. J. Inglese at NCATS to devise a new method for discovery and analysis of RNA-interacting small molecules. This method addresses one of the central problems in RNA-ligand interaction analysis, namely, the close coupling between cation binding, rna folding and ligand binding. To do this, the method employs commonly available instrumentation (qPCR machines) to perform a rapid, multidimensional analysis of the complex folding and binding landscape of an RNA, as a function of ligand concentration.
