Rhodium HTS
Rhodium HTS 380E9-X9
Docking resolution 1.7 A
Number of poses minimized per conformer : 38 , automatically determined by Rhodium
Number of conformers per ligand: 30
Scoring method: Linear regression model developed from known ligands through crystal structure poses and known affinities.
Scoring function: Regression model using ligand pose center of mass and number of ligand close contacts.
Pymol was used to add hydrogens to pdb protein models using default parameters.
Rigid-body ligand conformational libraries were generated using openbabel GA method with default parameters.
All binding site residues were fixed as were the conformers used in the rigid-body docking.
Poses were based on a cavity occupancy score (CAVOC) that counts the number of atomic contacts and thus the "shape match" of a pose to the enzyme.
Such poses may not be optimal (minimized) by the docking score, in other words these are not docking-score minimized poses, but other poses derived
from the "manifold" of rigid-body docked poses.
A CatS-specific scoring method, as derived in a separate validation exercise using known CatS ligands, was used
to rank poses. The model was developed using docking scores known ligands (~2000, derived from BindingDB.org) in the 3iej crystal structure.
The regression model uses the docking score of the pose, the cavity occupancy score, and the number of "unsatisfied" hydrogen bond donors and acceptors of the ligand in that pose.
No
Rhodium HTS
Rhodium 380E9-X9/ Openbabel 2.3.90 / pymol 1.3
Ligand SMILES to sdf by openbabel --gen3D
Ligand sdf optimization by openbabel obminimize -n 20000 -ff MMFF94
Ligand conformers generated by openbabel GA method
Protein pdb files prepared with pymol by adding H atoms
Pymol was used to add hydrogens to pdb protein models using default parameters.
Rigid-body ligand conformational libraries were generated using openbabel GA method with default parameters.
All binding site residues were fixed as were the conformers used in the rigid-body docking.
Several the 3iej crystal structure of the kinase was docked with the Rhodium HTS method.
This crystal structure was selected based on separate model validation exercises.
Rhodium HTS method. Poses of maximum cavity filling (by Rhodium CAVOC score) were selected from a manifold of minimzed poses.
Poses were selected based on the best score called "KRh Scorpio" previously derived from training set consisting of holo crystal structures and ITC free energy in the SCORPIO database.
No
Yes