Tutorial - Prepare a ROCS X 3D Library

This tutorial covers how to prepare a ROCS X library with the Multi-Stage ROCS X Preparation Floe. The multistage floes work by launching one “head” job that orchestrates the running of successive “stage” floes. As each stage floe processes work and completes, it automatically passes its results to downstream stages for further processing. Results from the stage floes can be used like normal resources on Orion outside of the multistage floes context. Stage floes are typically run using more defaults and fewer adjustable parameters. Although these defaults work well in most cases, users who require additional control can run the stage floes individually. More information on the individual floes can be found in the How-To Guides and in the floe documentation.

All inputs for the tutorials can be found in Organization Data / OpenEye Data / Tutorial Data / ROCS X Floes.

Prepare a ROCS X 3D Library

A ROCS X 3D Library can be prepared with the Multi-Stage ROCS X Preparation Floe, which runs the following floes in sequence:

• Reaction & Reagent Database - Create from BULK SMILES Floe

• Reaction & Reagent Database - Directory Listing Floe

• Reaction & Reagent Database - Parallel Export Synthon Collection Floe

• Reaction & Reagent Database - Synthon Collection Directory Listing Floe

• ROCS X - Prepare 3D Library

Launch the Head Floe

1. Navigate to the Multi-Stage ROCS X Preparation Floe on the Floe page. Click on “Launch Floe” to bring up the Job Form.

2. Modify the Name and Output path to your liking. Note the Unique Orchestration Job Tag (MS:ROCSX_Prep by default) under Orchestration Settings. This tag is applied to this job and all launched jobs for easy identification. This tag will be truncated to 64 characters.

3. Under Stage 1: Building Block SMILES Ingestion, enter these values into these parameters:

   • Reaction Definition File: Click “Choose Input” to load the reaction definitions used for building the Reaction & Reagent Database. For the tutorial, use Tutorial-rxndefs.txt.

   • VendorA SMI File(s): Load a SMI file containing vendor building block information. For the tutorial, use Tutorial-Enamine-BBs.smi.gz.

   • Fill out the rest of the VendorA parameters. VendorA ID will be the key for the vendor, so keep this short and distinct. Example parameters for the Enamine building blocks are shown below:

   

   Figure 1. Stage 1: Building Block SMILES Ingestion parameters.

4. Optionally, you may add more building blocks under Stage 1: Additional Building Block Sources. For the tutorial, use Tutorial-Molport-BBs.smi.gz to add building blocks from Molport to the library.

   

   Figure 2. A second vendor was added in Stage 1: Additional Building Block Sources.

5. Optionally, you may include deprotection transforms to add transformed synthons to the library (the library will include both the transformed and untransformed forms). Under Stage 2: Export 2D Synthon Library:

   • Deprotection Transforms: Load deprotection definitions here. For the tutorial, use Tutorial-deprotections.txt.

6. Leave the rest of the inputs for Stage 2 and Stage 3 blank. The head Multi-Stage Floe will fill these in automatically as stages complete (Stage 2 inputs will be loaded with results from Stage 1 when it completes, and so on).

   

   Figure 3. Stage 2: Export 2D Synthon Library parameters.

7. Label the outputs to your liking and click the “Start Job” button.

Evaluate the Results

While your jobs are running, you should see the Multi-Stage ROCS X Preparation job you launched in the Jobs tab on the Floe page. This is the head job that will coordinate the launching of the stage jobs, all of which will be labeled with the same Unique Orchestration Job Tag.

Note

The tutorial jobs should take ~4 hours to complete and cost approximately $20.

When your jobs have finished, you should see “Success” for the head job and all five stage jobs.

Figure 4. The completed Multi-Stage ROCS X Preparation jobs.

The head job collects the reports and results from the stage jobs. On the Jobs tab, click on the name of the head job (Multi-Stage ROCS X Preparation-ROCS X Quick Start in Figure 4). On the Details panel, there are expandable menus for Reports and Results. Click the “Open Report” icon for any report you want to examine, and it will open in a new tab.

The Status Report includes information about the cost of each floe.

Figure 5. Example costs for running the Multi-Stage ROCS X Preparation Floe.

Click the “View In Project Data” button next to Results to see key outputs that were generated from the multi-stage preparation. Hover your mouse over the “i” information icon to display metadata about a collection. The Type Hints metadata shows information about the number of synthons and products in the library.

Figure 6. Output for the Multi-Stage ROCS X Preparation Floe.

Tip

The cost of the running the ROCS X - Prepare 3D Library Floe is approximately proportional to the number of synthons in the 2D Synthon Library (rather than the number of products). Viewing the Type Hints in the Orion UI can be a quick way to estimate the cost of preparing the 3D library.

Note

In certain cases, you may want to skip the early stages of the multistage process and start from an intermediate stage. For example, you may want to rerun a ROCS X search in Stage 2 on the same model with different settings without initializing the model again in Stage 1. The Multi-Stage Floes start where they first receive input. To skip Stage 1, simply leave the input parameters for Stage 1 blank and provide input to Stage 2. The Multi-Stage Floe will skip Stage 1 (since it received no inputs for Stage 1) and start with the inputs provided in Stage 2.

The ROCS X 3D Search Library Collection is the final preparation output that will be used for search in the next section.