Figure 5 | Scientific Reports

Figure 5

From: Atomistic simulations shed new light on the activation mechanisms of RORγ and classify it as Type III nuclear hormone receptor regarding ligand-binding paths

Figure 5

The RORγ-LBD-co-activator complex final structure for one of the apo simulations is represented in blue (the co-activator is properly docked thanks to the correct positioning of H12). The simulations of agonist compound (A) 5-LBD and (C) 4-LBD complex in absence of co-activator still show a correctly positioned H12. However, inverse agonist compound (B) 10-LBD and (D) 9-LBD complex in absence of co-activator leads to a conformational transition, where H12 invades the docking site for co-activator, precluding its binding (marked with an asterisk). For both MMP, this is seen for all 4 independent simulations of the same system in the absence of co-activator represented in gray, red, green and magenta color, respectively. Dynamic motion capturing helix H12 mobility is exemplified by the first Principal Component for the system in absence of co-activator for (E) agonist 5-LBD and (F) inverse agonist 10-LBD.

Back to article page