title: Methods to enable the design of bioactive small molecules targeting RNA.
abstract: RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including structure-activity relationships through sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome.
authors.affiliation: The Department of Chemistry, The Scripps Research Institute, 130 Scripps Way #3A1, Jupiter, FL 33458, USA. Disney@scripps.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Disney
authors.forename: Ilyas
authors.initials: I
authors.lastname: Yildirim
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Childs-Disney
mesh_terms: D000818:Animals; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012313:RNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries; D012313:RNA