Dock One Million Molecules with the Gigadock Floe

In this tutorial, one million molecules will be selected at random from a database provided by OpenEye and docked to the heat shock protein 90 (HSP90) target using the Gigadock Floe. Running all the floes in this tutorial will cost approximately $30 (depending on current AWS pricing).

This tutorial uses the following floes:

Note

If you have not created a tutorial project or prepared the HSP90 heat shock protein 90 (HSP90) target (using crystal structure 1uyg) to create the hsp90_design_unit dataset, please go to the Preliminary Setup Tutorial before beginning this tutorial.

Prepare One Million Input Molecules

Molecules must be conformer expanded and placed in a collection (see Data Storage: Datasets, Files, and Collections) before they can be docked with the Gigadock Floe. Use a collection found on Orion in Organization Data/OpenEye Data/Gigadock Collections. In this tutorial, a new collection containing a random subset of ~1 million molecules from the selected collection will be created.

Locate the Filter Collection Floe on the Workflows tab in the Floe page.

Click “Launch Floe” to bring up the Job Form and set the following parameters.

  • Output Path: Use Tutorial/My Data/HSP90 Dock as the path.

  • Inputs

    • Input Collection: Click the “Choose Input” button. A Select Dataset modal will pop up. Follow the path Organization Data/OpenEye Data/Gigadock Collections and select an appropriate collection for your needs. To run the most affordable example for this tutorial, select the smallest collection. Click the “Use Collection as Input” button.

  • Outputs

    • Filtered Collection Name: Enter Tutorial 1M Gigadock Collection in the box.

  • Options

    • Keep This Fraction: Enter the fraction of molecules from the input collection needed to make an output of ~1M.

      Note

      We want to keep ~1M of the initial X input molecules, so 1/X = desired fraction. For example, the fraction for a collection of 25M molecules would be 1/25 = 0.04.

Click “Start Job” to begin the floe. With an input of approximately 3M molecules, the job will take about 30 minutes to run and cost approximately $1.

Dock Molecules to Site

Locate the Gigadock Floe on the Workflows tab of the Floe page. Click the “Launch Floe” button to bring up the Job Form and set the following parameters.

  • Output Folder: Enter Tutorial/My Data/HSP90 Dock into the box.

  • Inputs

    • Design Unit Or Receptor Dataset(s): Click the “Choose Input” button and use the hsp90_design_unit dataset with the protein prepared by the SPRUCE - Protein Preparation Floe when you uploaded 1UYG.

    • Input Conformer Collection: Click the “Choose Input” button and use the Tutorial 1M Gigadock Collection output from the Filter Collection Floe that you ran in the previous step.

  • Outputs

    • Hit List Dataset: Enter Hit List in the box.

    • Output Design Unit(s) Dataset: Enter Receptor in the box.

Note

The maximum recommended output contour volume is 1000 Å3. The size of the active site is strongly correlated with the time and cost of docking. The floe will fail if the Maximum Receptor Volume parameter is greater than the default 2050 Å3. For more information, see the Control the Cost of a Gigadock Run Explanation and the Estimate the Cost of a Gigadock Run How-To Guide.

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Figure 1. The Job Form for the Gigadock Floe with the input parameters set for docking one million molecules to the HSP90 target.

Click “Start Job” to begin the floe. The job should cost less than $30 (with Maximum Receptor Volume = 1000 Å3). Wait for the floe to complete before continuing with the Cluster Hit List Poses from Gigadock tutorial.