Rhodium HTS / Center-of-mass guided
Rhodium HTS 380E9-X9
Docking resolution 1.7 A
Number of poses minimized per conformer : 8
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.
The docking method and protocol were similar to those used in GC2 and were refined during the course of several weeks of CELPP trials.
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 conformers were then geometry optimized with the obminimize program, using default parameters.
All binding site residues were fixed as were the conformers used in the rigid-body docking.
The GC3-provided SO4 bound CatS structure was selected as the protein model. 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 docked poses of known ligands in the CatS SO4-bound structure provided by GC3. Coordinates of the center of mass of known holo ligand poses, aligned to the SO4 structure, were used to locate starting site in the protein for docking.
No
Rhodium HTS / Center of mass guided
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
Ligand conformers further optimized by openbabel obminimize
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 conformers were then geometry optimized with the obminimize program, using default parameters and the MMFF94 forcefield.
All binding site residues were fixed as were the conformers used in the rigid-body docking.
After analysis of several docking simulations using known ligands and holo CatS crystal structures, the GC3-provided SO4 bound CatS structure was selected as the best model
in reproducting known ligand pose geometries. Coordinates of the center of mass of known holo ligand poses, aligned to the SO4 structure, were used to locate starting site in the protein for docking.
Rhodium HTS method, starting poses guesses were centered on the expected ligand center of mass determined from analysis of non-covalent ligands in the Protein Data Bank.
Poses were selected based on the best docking score. The topmost scoring pose was selected, and re-scored using a CatS-specific regression model.
No
Yes