Computational Drug Discovery and Design

2. The “cleaned” chemical library is then submitted to rigid-
   receptor docking on a set of receptor’s representative structures
   (extracted as previously described from MD trajectories).
   When defining the receptor molecular entity, it should be
   kept in mind that water molecules might be important for
   ligand recognition and binding, although this is difficult or
   even impossible to predict. It might therefore be useful to
   run virtual screening several times both with and without
   selected water molecules in the putative ligand binding site.
   The volume within which the search for the optimal ligand
   position will be performed has to be defined by creating a box,
   characterized by the coordinates of its center and the sizes in
   each dimension. This can easily be done with the “make_re-
   ceptor” GUI of the OpenEye software. Walking through the
   “Molecules,” “Box,” “Shape,” and, optionally, the “Con-
   straints” menus will create all information necessary for the
   docking. Save the result in an .oeb file (.oeb.gz if compressed).
   If using Vina, generate a grid for each receptor structure with
   the AutoDock Tools. By doing this, you will place the center of
   the grid at the pocket’s center of mass and use a spacing of 1 A ̊.
   Save the grid size and coordinates for the use in docking
   configuration input files.
   Docking with OpenEye can be accomplished with the
   following example of a command line:

fred -rec rec.oeb.gz -dbase drugs.oeb.gz -dock_resolution

High \

-hitlist_size 100 -numposes 20

Note that the product of hitlist_size and numposes should not

exceed 10000. The command above uses a set of options, whose

default values are listed below:

-docked docked.oeb.gz

-undocked undocked.oeb.gz

-score score.txt

-report report.txt

-settings settings.param

-status status.txt

-annotate false (for VIDA display; per atom score breakdown)

-prefix fred (prefix of all output files)

It is also possible to launch the docking in parallel, on multiple

CPUs. For example, to launch docking on N processors, replace the

“fred” command with “oempirun -np N fred”.

Docking with Vina can be performed on multiple CPU cores,

but the program has been parallelized under OpenMP

162 Gre ́gory Menchon et al.