Breed Panel
Generate new ligand structures from a set of aligned ligands by swapping groups whose bonds overlap. Multiple rounds ("generations") of swapping can be made to generate new molecules in which multiple groups have been swapped with other molecules.
To open this panel, do one of the following:
- Click the Tasks button and browse to Enumeration and Ideation → BREED Ligand Creation
- Click the Tasks button and browse to Ligand Preparation and Library Design → Enumeration → BREED Ligand Creation
- Using
- Features
- Additional Resources
Using the Breed Panel
The BREED algorithm (J. Med. Chem.2004, 47, 2768–2775) generates new ligand structures from a supplied set of ligands. The ligands must be all in the same frame of reference, which can be achieved, for example, by aligning the binding sites of protein-ligand complexes, or from docking runs. The alignment is necessary for the algorithm, as it allows the identification of groups that are bonded in the same spatial location to the ligand core, and can be considered candidates for swapping.
A group from one ligand can be swapped with a group from another ligand if the bond to the group in the first ligand overlaps with the bond to the group in the second ligand. The bonds are considered to overlap if the angle between the two bonds is less than a specified maximum value and the atoms at each end of the bond in the first ligand are no further away from the corresponding atoms in the second ligand than a specified maximum value. Further constraints are that the bond is of the same order, and that it is not in a ring.
A new pair of molecules is produced for each overlapping bond in each input pair of molecules, with elimination of duplicates. This means that each new molecule has had only one group swapped. This constitutes one "generation" of swapping. In the next generation, the output molecules from the first generation are used as input, to produce structures with two swapped groups, and so on. You can specify the number of generations, which should be no more than the maximum number of overlapping bonds.
Breed Panel Features
- Use structures from option menu
- Open Project Table button
- File name text box and Browse button
- Maximum atom-atom-distance text box
- Maximum angle text box
- Number of generations text box
- Untangle structures option
- Swap terminal bonds option
- Job toolbar
- Status bar
- Use structures from option menu
-
Choose the structure source for the current task.
- 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.
- File—Use the specified file. When this option is selected, the File name text box and Browse button are displayed.
- 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.
- Open Project Table button
-
Open the Project Table panel, so you can
- 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.
- Maximum atom-atom-distance text box
-
Specify the maximum distance between the atoms at each end of an overlapping bond. If bond A–B in the first structure overlaps with bond C–D in the second structure, the distance between A and C and the distance between B and D must be less than the specified value.
- Maximum angle text box
-
Specify the maximum angle between bonds in two structures for the bonds to be considered to overlap.
- Number of generations text box
-
Specify the number of rounds (generations) of swapping of groups to perform. In each generation, a swap is made for each overlapping bond in each pair of molecules, to produce a pair of structures for each swap. The results are used as input to the next generation, to produce molecules with groups from multiple original source molecules. The maximum number of generations that can create new structures is equal to the maximum number of overlapping bonds in the original structures. The number of generations is restricted to 1 or 2.
- Untangle structures option
-
If the swapping of groups results in tangled structures, untangle them using LigPrep.
- Swap terminal bonds option
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Include terminal bonds in the swapping procedure, i.e. bonds to hydrogens and halogens.
- Job toolbar
-
Manage job submission and settings. See Job Toolbar for a description of this toolbar.
The Job Settings button opens the Breed - 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. 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.