Control the Cost of a Giga Docking Run
Context
Running the Gigadock floe on billions of molecules generally incurs significant computational cost. Typically a Gigadock on 2-3 Billion molecules cost approximately $30K, although there is significant variance depending on the characteristics of the target and molecules being docked and some runs could cost >$100K or as low as $10K.
This describes what factors affect the time an cost of a Gigadock and what adjustments an end user can make to adjust those factors.
Receptor / Design Unit
Size of the active site
The size of the active site is strongly correlated with the time and cost of docking and reducing the size of the active site will reduce the docking time and cost. The most relevant measure of active site size is the volume of the outer contour, which is a volume complementing the active site which all heavy atoms of docked poses must fit within. The outer contour can be visualized within Orion, but as of this writing the volume cannot be adjusted or measured within Orion. To measure or adjust the outer contour volume see the Edit a Receptor howto.
Note
For Gigadocking the maximum recommended output contour volume is 1000 cubic Angstroms.
The shape of the outer contour is used to filter the poses of a molecule whose conformers have been exhaustively rotates and translated within the active site. After this filtering the poses are all scored, which consumes the vast majority of the computational cost relative to the outer contour filter. Increasing the outer contour volume increases number of poses that need to be scored, thus increasing the time and cost of the docking. This effect is particularly sever in large active sites where the outer contour encloses large amount of solvent space not particular near the protein surface. In this case large numbers of poses that interact mostly with solvent pass the outer contour and get scored.
Docking Constraints
Adding one or more docking constraints to the receptor/design unit will reduce the time and cost of docking. The more constraints added the more the docking time and cost will be reduced, although there is a diminishing effect of additional constraints. While constraints are visible in Orion’s 3D window they cannot be added, deleted or adjusted within Orion as of this writing. To add, delete or adjust constraints see the Edit a Receptor howto.
Docking constraints filter out poses that do not make interactions with the active site specified by the constraint(s). This happens after the docking molecule’s conformers are exhaustively rotated and translated with the site and the resulting poses filtered by the outer contour (see previous section), but before the poses are scored. The vast majority of the computational time goes to the scoring, so filtering out more poses by adding constraints improves the speed of the docking. The more restrictive the constraint(s) the more poses get filtered before scoring and hence the faster the docking speed.
Docking Mode
The selected docking mode affects the time and cost of a Gigadock run. The Gigadock has three docking modes (see the ‘Dock Method’ parameter under Options in the Gigadock floe). The relative speed of these three methods from slowest (highest cost) to fastest (lowest cost) is
Fred
Hybrid
The default method is ‘Fred’.
Docking Molecules
Number of Molecules
The overall time and cost to run a Gigadock job is proportional to the number of molecules docked. So docking a smaller set of molecules will generally be faster.
Note
The size and number of conformers of docking molecules also influences the how fast they dock. It is possible that a small set of large floppy molecules could dock faster than a larger set of small rigid molecules.
Filtering Molecules
The number of molecule to dock can be reduced (and hence the cost of a Gigadock run lowered) if there are known molecular properties the docked molecules must have. The Filter Collection can be used to filter and existing docking collections based on a variety of molecular properties. Alternatively if the docking collection is being created from scratch from a SMILES or other file the same set of filtering options is available in the Prepare Giga Collections floe.