Fig. 6
From: Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes
PK4C9 directly causes opening of 5′ ss TSL2 residues and indirectly induces triloop conformation. a Bundle of 40 NMR structures of TSL2. b Representative ligand-free pentaloop (TSL2pent, silver) and triloop (TSL2tri, orange) NMR structures of TSL2. c Comparison of the mobility of TSL2pent and TSL2tri residues in 100-ns molecular dynamics (MD) trajectories, measured by root-mean-square fluctuation (RMSF). d Representative model structure of the binding mode of PK4C9 (green) to TSL2pent (TSL2pent-PK4C9, grey), taken from the most abundant cluster of a 100-ns MD trajectory. e Close-up 2D view of the binding mode of PK4C9. Interactions were plotted using the Maestro software. f Graph showing the PK4C9-induced increase in the distance between the C1’ atoms of residues A1 and U19 throughout the MD trajectory, as an indicator of terminal TSL2 opening. g Graph showing the PK4C9-induced decrease in the centre of mass distance between residues A8 and U12 throughout the MD trajectory, as an indicator of triloop formation. h Per-residue comparison of the mobility of TSL2pent-free and TSL2pent-PK4C9, measured by root-mean-square fluctuation (RMSF)
