Bioisostere Replacement Panel

Replace functional groups on a set of ligands with the corresponding bioisosteres, generating all single replacements.

To open this panel: click the Tasks button and browse to Enumeration and Ideation → Bioisostere Replacement.

  • Using
  • Features
  • Additional Resources

Using the Bioisostere Replacement Panel

Functional groups are replaced with bioisosteres that are defined in a resource file in the installation, which contains bioisosteres that are available in the literature. When the replacement is done for a given ligand, all replaceable functional groups are processed to produce a set of structures containing all single replacements. The structures are stored in an entry group that is named after the input ligand. The output structures are not minimized, so you should consider minimizing them before use in other applications.

If you want to use your own bioisosteres, you can do so from the command line:

[$SCHRODINGER/]run apply_transformations.py input-file output-file -r bioisostere-files

The default bioisostere file, transformations.json, is in the mmshare-v7.3 folder of your installation, in the data folder. You can copy and edit this file to add, remove or replace bioisostere transformations, or use it as a template. The bioisosteres are encoded as Reaction SMARTS (http://www.rdkit.org/docs/RDKit_Book.html#reaction-smarts), and are applied with the RDKit library. Along with the SMARTS pattern, you must provide a name and one or more tags (isostere group names). The -r option overrides the default, so you must list it explicitly to use it with the other files. Duplicate transformations are not eliminated when multiple files are used, so for efficiency you should ensure that your files have unique sets of transformations. However, duplicate structures are eliminated after the replacements are done.

Bioisostere Replacement Panel Features

Use structures from option menu

Choose the structure source for the ligands to be used for bioisostere replacement.

  • Project Table (n selected entries)—Use the entries that are currently selected in the Project Table or Entry List. The number of entries selected is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and select entries.
  • Workspace (n included entries)—Use the entries that are currently included in the Workspace, treated as separate structures. The number of entries in the Workspace is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and include or exclude entries.
  • File—Use the specified file. When this option is selected, the File name text box and Browse button are displayed.
Open Project Table button

Open the Project Table panel, so you can select or include the entries for the structure source.

File name text box and Browse button

Enter the file name in this text box, or click Browse and navigate to the file. The name of the file you selected is displayed in the text box.

Define immutable region from options

Define the region of the ligands that is excluded from replacements, i.e. is not changed. The choices are:

  • None—none of the ligand is excluded from replacements.

  • SMARTS—define the region by a SMARTS pattern. Enter or paste the SMARTS pattern in the text box, or click the Get from Workspace Selection button to load a SMARTS pattern from the selected atoms in the Workspace into the text box, where it can be edited.

Job toolbar

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

The Job Settings button opens the Bioisostere Replacement - 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.

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.

Tutorials

Related Topics