PL/MCT-tess descriptors and libSVM based pose prediction method
Discovery Studio 2017/Omega 2.5/OEDocking 3.0/ENTESS/libSVM/Matlab
Ionization: "rule-based" method (Discovery Studio)
No tautomer was generated.
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) Pose predictors were constructed using Omega/OEDdocking/Entess/libSVM prior to their application to the 24 test ligands.
Omega: number of confirmations=200 (default)
OEDocking: number of docking poses=1000
ENTESS (descriptors that characterized protein-ligand interface: PL/MCT-tess descriptors)
Pose predictors (libSVM)
For each one of 24 test ligands,
1) Structural similarity (Tc) based on MACCS fingerprints between this test ligand and 8 cognate ligands were calculated. The cognate ligands were ranked from the most similar one to the least similar.
2) The pose predictor that corresponded to the most similar cognate ligand (e.g. 3kwn) was applied to select native-like poses from 1000 binding poses generated by OMEGA and OEDocking. If none, the pose predictor corresponding to a less similar one was applied. This process ended till the native pose(s) were found for this test ligand.
3) The native poses were clustered with a RMSD threshold of 2 ? and the cluster centers were kept. For the situation in which more than 5 predicted native-like poses existed, Euclidian distances of the predicted native-like poses to the native pose were calculated and only 5 poses of smaller distances were submitted.
No
Yes