Name

ITScore_v1_TF

Software

ITScore_v1_TF

Parameters

grid = no

Method

A knowledge-based scoring function, ITScore_v2_TF, was used to evaluate these
binding models. The scoring function was originally developed with a statistical
mechanics-based iterative method using ia database containing 786 protein-ligand
complex structures, and was then calibrated using 974 small molecule-transcription factor
complexes from the SM-TF database with the iterative method.

Name

A ensemble docking method, XDZ_3

Software

MGLTools/AutoDock Vina 1.0/ITScore_v1_TF

System Preparation Parameters

maxconfs=500 #OMEGA
Gasteiger charges #Vina

System Preparation Method

All the released crystal structures of human FXR
protein-small molecule complexes were collected from the Protein Data Bank.
The co-crystal structures for FXR_1-FXR_36 provided by D3R were also included.
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 62 resulting crystal structures.
Preparation for docking with Vina was done using MGLTools,
in which the ligand PDB files generated with OMEGA were converted to the PDBQT
format by assigning partial charges and atom types.

Pose Prediction Parameters

Exhaustiveness=30 #exhaustiveness of global search (default=8)
Vina scoring function (empirical + knowledge-based function)
Num_modes=500 #max number of poses to generate
Re-scoring function, ITscore_v1_TF #a calibrated version of ITScore 1.0 using the SM-TF database

Pose Prediction Method

For a query compound, ensemble docking was performed using all the 62 FXR protein
structures collected from the PDB or provided by D3R. A modified version of AutoDock Vina was used for the sampling,
outputting up to 500 binding models for further evaluation. A knowledge-based scoring function, ITScore_v1_TF,
was used to evaluate these binding models. The scoring function was originally developed with a statistical
mechanics-based iterative method using a database containing 786 protein-ligand complex structures,
and was then calibrated using 974 small molecule-transcription factor complexes from the SM-TF database
with the iterative method.