Figure 4.

Comparison of FXR ligand binding modes and conformational changes of the binding pocket. (A) Binding modes of 5 (3dct) and its derivatives 14 and 16–18. Hydrophobic areas on the ligands are indicated in yellow, the charged interaction with Arg331 is depicted as red star, and H-bonds with Met265 and Arg331 are highlighted by red arrows. (B) Comparison of binding modes for 11 (black) and 15 using the 3fxv binding pocket. Compound 11 sterically clashes with the binding site in the 3fxv conformation. (C) Compound 13 fitted into the 3dct binding pocket, sharing a large part of it. The acidic functions differ in location and observed interactions. (D) Compound 12 fitted into the 3fxv binding pocket. The difluorophenyl moiety of 12 sterically clashes with the binding pocket conformation from 1fxv.