Rhodium HTS Mode


OpenBabel 2.3.90, Rhodium380E6-4 (propietary), PyMol 1.3

System Preparation Parameters

Openbabel standard option of --gen3D to create 3d structures from provided sdf files
Openbabel obminimize -n 20000 -ff MMFF94 for each ligand
Multiple rigid conformers from obabel --confab --rcutoff 0.7 --ecutoff 4

System Preparation Method

Selected protein structure models were downloaded from the RCSB website.
Next, hydrogen atoms were added with PyMol 1.3.
When multiple side-chain conformers were present, the first or "A" conformer was selected. Others were deleted from the .pdb file.
The prepared proteins were aligned to the provided apo template using the alignment tools available in PyMol.
Multiple rigid conformers (determined from the confab conformer generator) were docked in each of the downloaded protein models.

Pose Prediction Parameters

Default parameters were used.

Pose Prediction Method

Poses were predicted based on the minimized scoring function.
This includes an initial grid search for poses wherein trial poses are placed on a 3D grid of pose centers with resolution 1.7 Angstrom, surrounding the surface of the protein model.
Seventy-two trial poses (covering the SO3 rotation group) of each conformer are placed on each point, and scored
with a high-speed low-resolution, long-range potential similar to that of I. Vakser, et al.
Approximately the best 1% of those poses are refined with a docking score, based roughly on the XSCORE method, using the Multi Directional
Search of V. Torczon. This minimizer accounts for (or takes advantage of) chaotic behavior commonly found in pose optimization.