aaveo-LigandScoringProtocol.txt

Name

align_close

Software

Knime 2.12, LigPrep/ConfGen/Maestro 2016.3, MOE 2015.1001, Cresset Forge 10.4.2

Parameters

LigPrep pH 7.0
Tautomers generated and considered

Parameters

LigPrep pH 7.0
Tautomers generated and considered
Confgen, up to 100 confs
minimizedAffinity < 0
minimizedRMSD < 2.0

Method

System Preparation Method: Test set ligands were prepared using Schrodinger's LigPrep utility.
All inhibitor bound FXR structures were obtained from the PDB and aligned to the provided apo crystal structure.
Only aligned chains to the provided structure were retained (not other chains in the asym. unit). These were removed manually in Maestro.
The receptor (with water) and ligand were split using Schrodinger's tools.
For each test set ligand, the most simlilar ligand from the PDB set was identified using MOE's Most Similar Molecule(s) Knime node
using the MACCS fingerprint with the Tanimoto distance.

Pose Prediction Method

For each test set compound, conformers were generated using ConfGen from Schrodinger.
The conformers were aligned to the most similar crystal ligand using Forge from cresset. The aligned conformers were
minimized to the cooresponding co-crystal receptor using smina with default minimization settings.
The resulting conformers were manually examined and the "best" pose was identified based on alignment with the crytal ligand
and contacts with the crystal receptor.

The compounds were ranked based on the smina predicted affinity of this "best" pose.

aaveo-PosePredictionProtocol.txt

Name

align_close

Software

Knime 2.12, LigPrep/ConfGen/Maestro 2016.3, MOE 2015.1001, Cresset Forge 10.4.2

System Preparation Parameters

LigPrep pH 7.0
Tautomers generated and considered

System Preparation Method

Test set ligands were prepared using Schrodinger's LigPrep utility.
All inhibitor bound FXR structures were obtained from the PDB and aligned to the provided apo crystal structure.
Only aligned chains to the provided structure were retained (not other chains in the asym. unit). These were removed manually in Maestro.
The receptor (with water) and ligand were split using Schrodinger's tools.
For each test set ligand, the most simlilar ligand from the PDB set was identified using MOE's Most Similar Molecule(s) Knime node
using the MACCS fingerprint with the Tanimoto distance.

Pose Prediction Parameters

Confgen, up to 100 confs
minimizedAffinity < 0
minimizedRMSD < 2.0

Pose Prediction Method

For each test set compound, conformers were generated using ConfGen from Schrodinger.
The conformers were aligned to the most similar crystal ligand using Forge from cresset. The aligned conformers were
minimized to the cooresponding co-crystal receptor using smina with default minimization settings.
The resulting conformers were manually examined and the "best" pose was identified based on alignment with the crytal ligand
and contacts with the crystal receptor.

The compounds were ranked based on the smina predicted affinity of this "best" pose.