Automated Reaction-Based Enumeration Panel

Enumerate compounds based on multiple synthetic routes, with filtering on similarity to a reference compound, on properties, and on SMARTS-defined functional groups.

To open this panel: click the Tasks button and browse to Enumeration and Ideation → Automated Reaction-Based Enumeration.

  • Overview
  • Using
  • Features
  • Additional Resources

Overview of Automated Reaction-Based Enumeration

This panel automates processes in the Reaction-Based Enumeration Panel, taking default values for many of the options available in that panel. A PathFinder analysis of the input compound is performed with a default depth of 2; reaction paths are chosen at random from the results of the analysis, up to the maximum set; and the default reactant sets from the distribution are used for the enumeration. The same property and SMARTS filters are available, and in addition there is a similarity filter, which either keeps or discards compounds with a given similarity to a reference compound. The similarity is evaluated as the Tanimoto similarity between the topological fingerprints generated by RDKit with default settings (see here for details). The fragments (reactants) used in the enumeration come from the eMolecules building block library.

Using the Automated Reaction-Based Enumeration Panel

The compound input is the same as in the Reaction-Based Enumeration Panel — Choose Reaction Step, where you can load a compound and select regions of the molecule to exclude from the enumeration. The remaining tasks are to put limits on the number of reaction pathways and number of products, and set up any filtering of the output compounds.

If you are interested in finding highly similar compounds for lead optimization, you can set the similarity filter to keep a small percentage of the most similar compounds. If you want to avoid compounds that are similar to another compound, you can set the similarity filter to discard a large percentage of products that are most similar to that compound.

Automated Reaction-Based Enumeration Panel Features

Use compound from option menu

Specify the source of the compound for the analysis and enumeration:

  • Project Table (selected entry)—Use the entry that is currently selected in the Project Table. Only one entry must be selected. When this option is selected, the Load button is displayed.
  • Workspace—Use the entry that is currently included in the Workspace. Only one entry must be included in the Workspace. When this option is selected, the Load button is displayed.
  • File—Read the structure from a file. When this option is selected, the Browse button is displayed.
Load button

Load the compound from the Project Table or Workspace into the panel.

Browse button

Click Browse and navigate to the file you want to use for the source compound. The first structure in the file is used, so you should ensure that this structure is a ligand-sized molecule.

Compound display area

This area displays a 2D structure of the loaded compound. The bonds that can be broken in the reaction analysis are displayed when the pointer is in this area. These bonds define different regions of the molecule that can be enumerated. Click to select a region of the molecule to be excluded from the enumeration; Shift+click to auto-select other regions. The excluded regions are highlighted. You can choose the core of a compound to enumerate peripheral groups, or choose peripheral groups to enumerate the core, or a mix of both.

Pathfinder options section

Specify options for the PathFinder analysis of reaction paths and filtering the products of the enumeration.

Property Filter button

Filter the products of the enumeration by ranges of property values. Opens the Filter Options Dialog Box.

SMARTS Filter button

Filter the products of the enumeration by matches to SMARTS patterns. Opens the Filter by SMARTS Dialog Box.

Maximum number of pathways text box

Specify the maximum number of reactions to use in the analysis of the designated compound.

Maximum number of products text box

Specify the maximum number of products to generate in the enumeration.

Job toolbar

Manage job submission and settings. See Job Toolbar for a description of this toolbar.

The Job Settings button opens the Automated Reaction-Based Enumeration - Job Settings Dialog Box, where you can make settings for running the job.

Status bar

The status bar displays information about the current job settings and status for the panel. The settings includes the job name, task name and task settings (if any), number of subjobs (if any) and the host name and job incorporation setting. The job status can include messages about job start, job completion and incorporation. It also displays a progress bar for the job.

Use the Reset button to reset the panel to its default settings and clear any data from the panel. You can also reset the panel from the Job toolbar.

The status bar also contains the Help button , which opens the help topic for the panel in your browser. If the panel is used by one or more tutorials, hovering over the Help button displays a button, which you can click to display a list of tutorials (or you can right-click the Help button instead). Choosing a tutorial opens the tutorial topic.

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