Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs.
The development of small molecules that target RNA is challenging yet, if successful, could advance the development of chemical probes to study RNA function or precision therapeutics to treat RNA-mediated disease. Previously, we described Inforna, an approach that can mine motifs (secondary structures) within target RNAs, which is deduced from the RNA sequence, and compare them to a database of known RNA motif-small molecule binding partners. Output generated by Inforna includes the motif found in both the database and the desired RNA target, lead small molecules for that target, and other related meta-data. Lead small molecules can then be tested for binding and affecting cellular (dys)function. Herein, we describe Inforna 2.0, which incorporates all known RNA motif-small molecule binding partners reported in the scientific literature, a chemical similarity searching feature, and an improved user interface and is freely available via an online web server. By incorporation of interactions identified by other laboratories, the database has been doubled, containing 1936 RNA motif-small molecule interactions, including 244 unique small molecules and 1331 motifs. Interestingly, chemotype analysis of the compounds that bind RNA in the database reveals features in small molecule chemotypes that are privileged for binding. Further, this updated database expanded the number of cellular RNAs to which lead compounds can be identified.
Department of Chemistry and ‡Informatics Core, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Matthew D
MD
Disney
Department of Chemistry and ‡Informatics Core, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Audrey M
AM
Winkelsas
Department of Chemistry and ‡Informatics Core, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Sai Pradeep
SP
Velagapudi
Department of Chemistry and ‡Informatics Core, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Mark
M
Southern
Department of Chemistry and ‡Informatics Core, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Mohammad
M
Fallahi
Department of Chemistry and ‡Informatics Core, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Jessica L
JL
Childs-Disney
D001483:Base Sequence; D015195:Drug Design; D006801:Humans; D048088:Informatics; D007612:Kanamycin / Q000031:analogs & derivatives / Q000737:chemistry; D035683:MicroRNAs / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
C557457:6'-N-5-hexynoate kanamycin A; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D054852:Small Molecule Libraries; D007612:Kanamycin; D012313:RNA