Figure 6
From: Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist
Modelling structural mobility with ensemble refinement. (a,b) Models of LRH-1 bound to either SS-RJW100 (a) or RR-RJW100 (b) generated through Ensemble Refinement, resulting in 35 coordinate models for the SS-RJW100-LRH-1 structure and 38 for LRH-1-RR-RJW100 (superposed in the figure). The input models for ensemble refinement were PDB 6VC2 (from this publication) with one conformation of SS-RJW100 modelled in the pocket and PDB 5L11, respectively35. The ensembles are represented as cartoon “putty,” in which the size of the cartoon is proportional to residue B factors. Insets depict close-up views of the ligand conformations in each model of the ensemble. (c) Left, Stability of hydrogen bonds made by the RJW100 hydroxyl groups was determined by measuring the distances between the hydroxyl groups and the closest binding interaction in each model of the ensembles. For SS-RJW100, we measured the distance between OH and M345 (sulphur atom), and for RR-RJW100 we measured the distance between the OH and the water atom coordinating residue T352. Grey shaded area indicates distances in hydrogen-bonding range. Right, Stability of π-π stacking with residue H390 was measured in each frame. Grey shaded area indicates distances in bonding range. (d) The intact water network contains four molecules, but this network is disrupted in the SS-RJW100 ensemble. The pie chart summarizes the number of water molecules in each model in the ensemble.
