koq0o-PosePredictionProtocol.txt

Name

PL/MCT-tess descriptors and libSVM based pose prediction method

Software

Discovery Studio 2017/Omega 2.5/OEDocking 3.0/ENTESS/libSVM/Matlab

System Preparation Parameters

Ionization: "rule-based" method (Discovery Studio)
No tautomer was generated.

System Preparation Method

1. "Prepare ligands" module in Discovery Studio was applied to add hydrogens to all 24 ligands and generate their protonated states ("rule-based" method).
2. The construction of pose predictors:
1) Cocrystal structures from PDB that contained non-covalent ligands and shared the same binding site were collected. All the waters in the cocrystal structures were deleted while "clean protein" tool in Discovery Studio was applied to prepare protein structures.
2) The cognate ligand of each cocrystal structure was kept and used to define the binding site. Each cognate ligand was then redocked against the binding site of the corresponding protein structure by Omega and OEDocking.
3) Those protein structures that can generate no more than 10 binding poses were excluded, thus 8 pairs of cognate ligands and protein structures (2f1g, 2r9m, 2r9n, 2r9o, 3iej, 3kwn, 4p6e and 4p6g) were used for building pose predictors.
4) 8 pose predictors were constructed using Omega/OEDdocking/Entess/libSVM prior to their application to the 24 test ligands.
5) PPE (pose predictor ensemble) was constructed by ensembling technique that used all the predictions from 8 pose predictors as inputs.

Pose Prediction Parameters

Omega: number of confirmations=200 (default)
OEDocking: number of docking poses=1000
ENTESS (descriptors that characterized protein-ligand interface: PL/MCT-tess descriptors)
PPE (libSVM)

Pose Prediction Method

For each one of 24 test ligands,
1) Each test ligand was docked against its corresponding receptor structure by OMEGA and OEDocking.
2) All docking poses (1000 poses per test ligand) were predicted by PPE, and the native-like poses were kept.
3) The native poses were clustered with a RMSD threshold of 2 A and the cluster centers were kept.
4) Euclidian distances of the predicted native-like poses to 8 native poses (from cocrystal structures from PDB) were calculated and only 5 poses of smaller distances were submitted.

Answer 1

No

Answer 2

Yes