Figure 7: Docking studies support the binding of 1 to MBNL1 and 2 to r(CUG) repeats.
From: Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules
(a) Extensive interactions are observed between MBNL1 and 1 at the RNA-binding pocket. The ethenyl group and the phenyl and thiofuran rings of 1 are stabilized by extensive cation–π interactions with arginine residues. The cation–π interaction between 1 and Arg195 is reminiscent of the MBNL1–RNA interaction34. The ligand binding pocket is shown as a transparent surface. Hydrogen bonds are shown as yellow dash lines. (b) Lowest free energy conformation of the 2–r(CUG) complex (binding mode p in Supplementary Table S5 and Supplementary Fig. S13). (b, top) RNA sequence used in MD simulations. Side (b, bottom left) and top (b, bottom right) views of the 2–r(CUG) complex. The yellow wireframe represents the molecular surface of compound 2. The RNA backbone is represented in light blue. For simplicity, hydrogen atoms are not shown. Note that in this binding mode, the interactions in the UU pair (green) are fully lost, and compound 2 stacks between the flanking GC base pairs (represented in red and blue).
