Cooperative binding of a quinoline derivative to an RNA stem loop containing a dangling end

The binding of a quinoline derivative (QD2) to a small RNA stem loop containing a 3'-dangling end (RNA1) has been studied. The compound was identified by first performing a similarity search of the NCI database of 250,000 compounds and then using computational docking with autodock to evaluate the binding of the resulting compounds to RNA1. Binding experiments using fluorescence and ITC methods revealed that QD2 binds cooperatively to four binding sites on RNA1 with equilibrium binding dissociation constants ranging from 8.2 (+/-0.3) to 12.5 (+/-4.2) microM. CD and UV titration experiments suggested that binding of QD2 changes the conformation of both RNA1 and the QD2 chromophore and stabilizes RNA1.