Probing Riboswitch Binding Sites with Molecular Docking, Focused Libraries, and In-line Probing Assays
Molecular docking calculations combined with chemically focused libraries can bring insight in the exploration of the structure–activity relationships for a series of related compounds against an RNA target. Yet, the in silico engine must be fueled by experimental observations to drive the research into a more effective ligand-discovery path. Here we show how molecular docking predictions can be coupled with in-line probing assays to explore the available chemical and configurational space in a riboswitch binding pocket.
Key wordsStructure-based Ligand design Virtual screening Structure–activity relationship (SAR) Docking Focused library In-line probing
This work was supported by the National Sciences and Engineering Research Council of Canada (NSERC). D.A.L. is a Canadian Institutes of Health Research (CIHR) New Investigator Scholar. F.C. was supported by the “Young SISSA Scientist” grant (FISB.647 2011) for independent research development. F.C. and G.B. acknowledge the European Research Council for funding through the Starting Grant S-RNA-S (no. 306662).
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