ljdjm-LigandScoringProtocol.txt

Name

glide_ensemble_docking

Software

Schrodinger software: glide, prepwizard, ligprep

Parameters

POSTDOCK_NPOSE 10 POSTDOCK_XP_DELE 5. POSTDOCKSTRAIN YES POSES_PER_LIG 5 MAXREF 800 RINGCONFCUT 2.5

Method

Automated Ensemble Docking approach using all structures available in the PDB plus structures released after stage 1
All PDB chains overlayed into reference apo structure
Proteins and ligands prepared with Schrodinger software

Preparation of docking grids
- use protein chains overlayed and prepared as above
- define cubical grid box that contains all ligands in x-ray structure
- calculate all grids using same box and mostly default parameters
- no waters considered

Ensemble docking workflow:
- dock each ligand against all grids using glide XP, keep max. 5 poses per ligand-receptor combination
- the pose with the best docking score was selected
- docking scores for the poses selected were used to rank the ligands

ljdjm-PosePredictionProtocol.txt

Name

glide_ensemble_docking

Software

Schrodinger software: glide, prepwizard, ligprep

System Preparation Parameters

ligprep assumed pH 7.4, stereochemistry from smiles
prepwizard -keepfarwat -disulfides -samplewater -propka_pH 7.0 -fix ${base}.pdb ${base}_prep.pdb
add side-chains, loops with -fillloops Ć¢fillsidechains

System Preparation Method

ligprep: keep stereochemistry defined by smiles, pH=7.4
protein preparation:
overlay all protein chains to apo structure, then prepare using prepwizard:
$SCHRODINGER/utilities/prepwizard -keepfarwat -disulfides -samplewater -propka_pH 7.0 -fix ${base}.pdb ${base}_prep.pdb
Process: assign bond orders; add H atoms; create disulfide bonds; sample water orientations; assign charge states at pH 7.0; minimize H atoms only
Fill missing loop & sidechains option: -fillloops Ć¢fillsidechains
Issues not covered: alternative residue conformation; occupancy etc.

Pose Prediction Parameters

POSTDOCK_NPOSE 10 POSTDOCK_XP_DELE 5. POSTDOCKSTRAIN YES POSES_PER_LIG 5 MAXREF 800 RINGCONFCUT 2.5

Pose Prediction Method

Automated Ensemble Docking approach using all structures available in the PDB plus structures released after stage 1
All PDB chains overlayed into reference apo structure
Proteins and ligands prepared with Schrodinger software

Preparation of docking grids
- use protein chains overlayed and prepared as above
- define cubical grid box that contains all ligands in x-ray structure
- calculate all grids using same box and mostly default parameters
- no waters considered

Ensemble docking workflow:
- dock each ligand against all grids using glide XP, keep max. 5 poses per ligand
- automated pose selection (using custom python script)
for each ligand merge poses from all grids and rank by XP glide docking score
pick pose with best XP glide docking score as best pose
select 4 additional pose by going down the ranked poses and picking new poses that are different enough from existing ones (using an RMSD cutoff of 1.0 A)