Pymol 1.8.4, Smina Apr 2 2016, idock 2.2.1, Yasara 16.11.20, Open Babel 2.3.2

System Preparation Parameters

Use pdb_redo for template preparation, Vinardo docking function with smina, RF v3 with idock for scoring after docking.

System Preparation Method

Visual analysis of FXR crystal structures in the PDB chose 5 representative structures: 3olf, 3l1b, 4qe6, 3p89, 3fli. Used re-refined structures from PDB_REDO for 3olf, 3p89, 3fli, 3l1b. Hydrogen atoms were added by OpenBabel. 3D structures of ligands were generated by OpenBabel.

Pose Prediction Parameters

Discard water molecules. Use smina to dock against region of ligand from crystal structure + 8A on each side. Use docking function Vinardo. Exhaustiveness = 64. Num_modes=9. Follow docking with energy minimization of ligand with smina using Vinardo function. Rescore all poses with idock using RF v3. Choose best scoring pose and energy minimize + simulated annealing with Yasara using Nova force field, without solvent.

Pose Prediction Method

Ligands were visually checked that they bound in a reasonable manner, in the orthosteric site. All top scoring poses were acceptable except FXR_11. The third highest score for FXR_11 was used instead.