Motivation: RNA molecules can fold into complex and stable 3-D structures, allowing them to carry out important genetic, structural, and regulatory roles inside the cell. These complex structures often contain 3-D pockets made up of secondary structural motifs that can be potentially targeted by small molecule ligands. Indeed, many RNA structures in PDB contain bound small molecules, and high-throughput experimental studies have generated large number of interacting RNA and ligand pairs. There are considerable interests in developing small molecule lead compounds targeting viral RNAs or those RNAs implicated in neurological diseases or cancer.
Results: We hypothesize that RNAs that have similar secondary structural motifs may bind to similar small molecule ligands. Towards this goal, we established a database collecting RNA secondary structural motifs and bound small molecules ligands. We further developed a computational pipeline, which takes input an RNA sequence, predicts its secondary structure, extracts structural motifs and searches the database for similar secondary structure motifs and interacting small molecules. We demonstrated the utility of the server by querying α-synuclein mRNA 5′ UTR sequence and finding potential matches which was validated as correct.
Availability and Implementation: The server is publicly available at http://RNALigands.ccbr.utoronto.ca. The source code can also be downloaded at https://github.com/SaisaiSun/RNALigands.
Macromolecular Scaffolds for Immobilizing Small Molecule Microarrays in Label-Free Detection of Protein−Ligand Interactions on Solid Support
