Gigadock Warp Details

Overview

The Gigadock Warp floe is designed to approximate a full Gigadock job at a fraction of the cost using a combination of docking and FastROCS. The input to Gigadock Warp is a design unit(s) and a collection(s) of molecules to dock, the same as the Gigadock floe. The ‘Chemgauss4’ (default), ‘Hybrid’ and ‘Fast Fred’ scoring method from Gigadock are also available in Gigadock Warp. The primary output of the Gigadock Warp is a 10K hit list of top scoring docked molecules.

Method

Gigadock Warp works as follows.

  1. Dock a random subset of molecules

  2. Cluster top docked molecules and select top scoring cluster heads

  3. Runs FastROCS on all input molecules using top scoring poses from the previous step as queries

  4. Re-dock the top scoring molecules from FastROCS

  5. Output Hit List of top scoring docked molecules.

gigadock_warp_flow_chart

Flow chart of how Gigadock Warp works. The hyper parameters for this floe are shown in bold with the default settings shown (these are adjustable in the floes advanced options).

Performance On HSP90 Compared to Gigadock

The results of a Gigadock Warp run are better, i.e., more similar to the results of a Gigadock the larger the number of molecule being docked.

Comparison of HSP90 Gigadock Warp and Gigadock Docking Results

Number of molecules docked

10 Million

140 Million

1.4 Billion

Fraction of Top 10K molecules in common

0.40

0.55

0.68

The number of molecules common to both hit lists is a function of the hit list size.

gigadock_warp_flow_chart

Fraction of molecules common to both the Gigadock Warp and Gigadock hit lists versus the size of the hit list.

Expected Cost

Docking a billion molecules with Gigadock Warp is expected to cost a few thousand dollars. Docking the same billion molecules with Gigadock is expected to cost a few tens of thousands of dollars. In general the cost of Gigadock Warp will be ~1/8th the cost of Gigadock (the Gigadock Warp docks 10% molecules, of Gigadock and running the FastROCS part is equivilent to docking about %2.5 of the molecule, hence 12.5% of the cost of Gigadock). These cost vary linearly with the number of molecules and by the characteristics of the active site (see Control the Cost of a Giga Docking Run for more detail).