RNALigands: a database and web server for RNA-ligand interactions

RNA molecules can fold into complex and stable 3D structures, allowing them to carry out important genetic, structural, and regulatory roles inside the cell. These complex structures often contain 3D 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 a large number of interacting RNA and ligand pairs. There is considerable interest in developing small molecule lead compounds targeting viral RNAs or those RNAs implicated in neurological diseases or cancer. We hypothesize that RNAs that have similar secondary structural motifs may bind to similar small molecule ligands. Toward this goal, we established a database collecting RNA secondary structural motifs and bound small molecule ligands. We further developed a computational pipeline, which takes as input an RNA sequence, predicts its secondary structure, extracts structural motifs, and searches the database for similar secondary structure motifs and interacting small molecule. We demonstrated the utility of the server by querying alpha-synuclein mRNA 5 ' UTR sequence and finding potential matches which were validated as correct. The server is publicly available at http://RNALigands.ccbr.utoronto.ca. The source code can also be downloaded at https://github.com/SaisaiSun/RNALigands.

Automated summary

RNA molecules can fold into complex three-dimensional structures and interact with small molecule ligands. Researchers have established a database of RNA secondary structural motifs and bound small molecule ligands. They also developed a computational pipeline to predict RNA secondary structures and search for similar motifs and interacting small molecules. The server was successfully used to identify potential matches for a specific RNA sequence.