align_close_mmgbsa
Knime 2.12, LigPrep/ConfGen/Maestro/Prime MM-GBSA 2016.3, MOE 2015.1001, Cresset Forge 10.4.2
LigPrep pH 7.0
Tautomers generated and considered
LigPrep pH 7.0
Tautomers generated and considered
Confgen, up to 100 confs
MMGBSA: Remove ligand strain: NO
MMGBSA: Protein Flexibility: 0.0 A
MMGBSA: Sampling Methods: Minimize
System Preparation Method: Test set ligands were prepared using Schrodinger's LigPrep utility.
All inhibitor bound FXR structures were obtained from the PDB and Phase 1 results crystals 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 or from the Phase 1 results crystals was identified using MOE's Most Similar Molecule(s) Knime node
using the MACCS fingerprint with the Tanimoto distance.
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 Prime MM-GBSA with default settings (as listed above).
The compounds were ranked based on the 'MMGBSA dG Bind' predicted affinity.
align_close_mmgbsa
Knime 2.12, LigPrep/ConfGen/Maestro/Prime MM-GBSA 2016.3, MOE 2015.1001, Cresset Forge 10.4.2
LigPrep pH 7.0
Tautomers generated and considered
Test set ligands were prepared using Schrodinger's LigPrep utility.
All inhibitor bound FXR structures were obtained from the PDB and Phase 1 results crystals 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.
Confgen, up to 100 confs
MMGBSA Remove ligand strain: NO
MMGBSA Protein Flexibility: 0.0 A
MMGBSA Sampling Methods: Minimize
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 Prime MMGBSA with default settings (as listed above).
The compounds were ranked based on the 'MMGBSA dG Bind' predicted affinity.