Gigadock Warp Floe 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 minimum input to the Gigadock Warp Floe is a design unit and a collection of molecules to dock, the same as the Gigadock Floe. The Chemgauss4 (default), Hybrid, and Fast-Fred scoring methods from Gigadock are also available in Gigadock Warp. The primary output of the Gigadock Warp Floe is a 10K hit list of top-scoring docked molecules.

Method

The Gigadock Warp Floe works as follows.

  1. Dock a random subset of 0.1% - 10% of the molecules.

  2. Construct a feature vector for all input molecules with the following:

    • FastROCS Combo and Shape Tanimoto similarities to the 100 top-scoring molecules from Step 1

    • Tree fingerprint bits

    • The following 2D properties and their squared and cross terms: Molecular Weight, 2D Polar Surface Area, XLogP, Number of Acceptors, Number of Donors, Number of Hydrogen Atoms, Number of Heavy Atoms, Number of Carbon Atoms, Number of Nitrogen Atoms, Number of Oxygen Atoms, Number of Fluorine Atoms, Number of Phosphorous Atoms, Number of Sulfur Atoms, Number of Chlorine Atoms, Number of Bromine Atoms, Number of Iodine Atoms, Number of Rotatable Bonds, Number of Bonds, Number of Heavy Bonds, Number of Single Bonds, Number of Heavy Single Bonds, Number of Double Bonds, Number of Triple Bonds, Number of Aromatic Bonds, Number of Rings, Number of Aromatic Rings

  3. Train a linear regression model of the docking score using the molecules from Step 1 and the features constructed in Step 2.

  4. Predict the docking score of all molecules not docked in Step 1.

  5. Dock 4% of the molecules with the highest predicted docking score.

  6. Write and output a hit list of the top-scoring molecules docked in either Step 1 or Step 5.

gigadock_warp_flow_chart

Figure 1. The flow chart for the Gigadock Warp Floe.

Performance Compared to the Gigadock Floe

Table 1. A Comparison of the Gigadock Warp Floe and Gigadock Floe Results for the Docking of 1.4 Billion Molecules.

Gigadock Cost

Gigadock Warp Cost

Molecules Common to Gigadock and Gigadock Warp 10K Hit Lists

Phosphodiesterase 5a (Fred)

$15,500

$1,900

93%

MCL-1 (Fred)

$35,400

$3,100

91%

MCL-1 (Hybrid)

$22,000

$2,500

90%

Mineralocorticoid Receptor (Fred)

$12,500

$1,900

75%

Mineralocorticoid Receptor (Hybrid)

$22,000

$2,300

72%