# Name for the protocol
Name: A template-based method, XDZ_0
#
# All software packages used and their versions:
Software: OMEGA 2.5/SHAFTS/AMBER11
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# List of key parameters used for system preparation
System Preparation Parameters: maxconfs=500 #OMEGA
#
# Plain-text description of system preparation method
System Preparation Method: All the released crystal structures of human 
FXR protein-small molecule complexes were collected from the Protein Data Bank. 
If there exist more than one PDB entries containing identical small molecules 
binding to the same pocket, the structure with a higher resolution was kept, 
resulting in a total of 26 resulting crystal structures.
Ligand conformational libraries were generated using OMEGA.  
#
# List any number of key computational parameters in the following lines:
Pose Prediction Parameters: AM1-bcc #atomic charges for ligands
Pose Prediction Parameters: AMBER03 force field
Pose Prediction Parameters: Generalized Amber force field (GAFF)

#
# Provide free text description of your method below. Use as many lines as you need. 
Pose Prediction Method: For a query compound, the SHAFTS program was employed to 
calculate its structural similarities (i.e., the shape-feature similarities) with 
the small molecules in the released FXR structures. The PDB entry that has the best 
similarity score with the query ligand was used as the template. If HybridScore < 1.2, 
only ShapeScore was used to rank the PDB entries. 
Then, the query compound was superimposed onto the ligand in the template. 
The protein-query compound complex was used as the initial structure for the next 
MD refinement with AMBER11. Atomic partial charges of each ligand were assigned using 
Antechamber based on the AM1-bcc method after ligand minimization. Using the Leap module, 
the AMBER03 force field and the Generalized Amber force field (GAFF) were applied to the 
receptor and to the ligand, respectively. The hydrogen atoms, water molecules and counter 
ions were also added to the complexes. The solvated complexes were then minimized in two steps. 
During the first step, the solvent molecules were minimized for 1000 steps via steepest descent, 
followed by 3000 steps via conjugate gradient.  A 500 kcal/mol/Å^2 restraint was imposed on all 
the protein atoms and ligand atoms. During the second step, the protein-ligand complexes and the 
solvent were both minimized for 10,000 steps via the steepest descent method, followed by conjugate 
gradient minimization until the energy gradient of the system converged to 0.01 kcal/mol/Å.

