Map Options Dialog Box

Set options for map generation and regenerate the map.

To open this dialog box, click Generate Map or Regenerate Map in the FEP+ panel.

  • Features
  • Additional Resources

Map Options Dialog Box Features

Ligands to use options

These options indicate which ligands will be used to generate the map: selected ligands, or all ligands, and can be used to change the choice, with some restrictions as explained below. If you are generating a map for selected ligands, the tool tip for the Selected option lists the titles of the ligands that are selected.

The ligands that are selected when you click Generate Map in the FEP+ panel are the ligands that will be used to generate the map. No changes are made to connections between other ligands. Changing the ligand selection does not automatically change the set used to generate the map; to change this set, you must click Generate Map in the FEP+ panel again, to register the new selection.

Being able to select different ligands allows you to do other things while setting up the map, such as placing a single ligand in the Workspace to define a SMARTS pattern for the core.

The Selected option is unavailable if there were no ligands selected or there was only one ligand selected when you clicked Generate Map. This selection means "generate the map for all ligands", as a map cannot otherwise be generated for 0 or 1 ligands.

Map topology type option menu

Choose the type of map topology to use when generating a map.

  • Optimal topology—Create a map in which the connections are determined for optimal performance of the FEP calculations (high similarity of the connected ligands).
  • Star topology—Create a map in which the ligands selected in the Bias column are connected to every other ligand, and the other ligands are not connected to each other. A warning is displayed if you do not have ligands selected in the Bias column.
Keep existing connections option

Keep the connections between the target ligand set (ligands to use for the map specified above) when generating the map. However, new connections are not added between ligands that are already connected when the new map is generated, but they are added between ligands that are not already connected. For example, connections would be added between two disconnected graphs but not within those graphs.

If this option is deselected, the existing connections between the target ligand set are discarded, but connections between other ligands are kept.

When you select this option, the Generate Map button changes to Update Map.

Define custom substructure option menu

Choose an item from this menu to provide one or more SMARTS patterns to define custom cores or linkers. The tools for providing the pattern are displayed when you select this option. See Using a Custom Core in the FEP+ Panel for more information.

  • None—Use the default, which is no custom core or linkers. By default, all atoms that can possibly be mapped to each other in two connected ligands are mapped, and used as the core. This minimizes the perturbation between the two ligands. This option should be used for fragment linking, as the fragments are automatically selected as the custom core.

  • Core—Define a custom core. The Generate Map button is disabled until a custom core is selected. This can be useful so that more atoms are included in the "hot" region that is sampled with reduced potentials. Once the custom core is defined for each ligand, the set of core atoms used for an edge is determined by mapping the atoms in one custom core to the atoms in the other custom core. If only one ligand has a custom core defined, the atoms in that custom core are mapped onto the set of all atoms in the other ligand.

    A given SMARTS pattern must match only once in each ligand. If there are multiple matches of a single SMARTS pattern, the pattern is ignored. If you provide multiple SMARTS patterns, all SMARTS patterns are tried on each ligand in order of size (number of atoms) and the first one that matches is used for the core. If there is no match, the default core definition is used.

    For covalently bound ligands, ensure that the C-alpha atom of the covalently bonded receptor residue is included in the pattern.

    You can mark the ligands that match the SMARTS pattern by selecting SMARTS matches from the Display perturbation properties button menu.

  • Linker—Define a linker between two parts of the molecule, for linker enumeration (not for linking fragments). The Generate Map button is disabled until a custom linker is selected.

    This option is not available for covalently bound ligands.

The tools for selecting the common substructure depend on the choice of substructure:

Select custom core SMARTS selection tools

When defining a custom core, enter one or more SMARTS patterns in the text boxes. You can type or paste a SMARTS pattern directly into a text box and modify it as needed. You can add additional SMARTS rows by clicking the add (+) button.

To generate a SMARTS pattern for a row instead of typing it, select the row and click the Load SMARTS link menu, then choose one of the following:

  • Workspace Selection—Generate a SMARTS pattern from the atoms selected in the Workspace. If you select atoms in more than one molecule, the first pattern is loaded into the selected row and a new row is added for each of the others.
  • Sketch—Open a Sketcher to draw a structure. When you close the Sketcher, a SMARTS pattern is generated for the sketched structure.

Click a SMARTS text box to select that row; only one row can be selected at a time. The Load SMARTS menu is available when a row is selected, or when there is a single empty SMARTS text box.

Each SMARTS row displays a matches indicator that shows how many ligands match the pattern. Hover over the indicator to see a few of the matching ligands, then click View all to open a dialog that lists all the matching ligands, each shown as a 2D structure with the matched substructure highlighted. You can also click the indicator to open this dialog directly.

Click the vertical dots to open a menu with the following options:

  • Show Full SMARTS / Collapse SMARTS—Expand or collapse the text box to show the full SMARTS pattern or a truncated version.
  • Copy to Clipboard—Copy the SMARTS pattern to the system clipboard.
  • View in Sketcher—Open a Sketcher to view or edit the structure for the SMARTS pattern.
  • Clear—Remove the SMARTS pattern from the text box.
  • Delete—Remove this SMARTS row. Only available when there are multiple rows.
Extend mapping option

If this option is selected, the custom core defined in the Select custom core SMARTS text box is extended to any R-groups that are matched.

Select custom linker SMARTS selection tools

To define a linker, click the Load SMARTS link menu and choose Workspace Selection to generate a SMARTS pattern from the atoms selected in the Workspace. The selected atoms must all belong to the same molecule. The SMARTS text box is read-only; you cannot type directly into it.

Click the vertical dots to open a menu with the following options:

  • Show Full SMARTS / Collapse SMARTS—Expand or collapse the text box to show the full SMARTS pattern or a truncated version.
  • Copy to Clipboard—Copy the SMARTS pattern to the system clipboard.
  • View in Sketcher—Open a Sketcher to view the structure for the SMARTS pattern.
  • Clear—Remove the SMARTS pattern.

The matches indicator shows how many ligands match the pattern. Hover over the indicator to see a few of the matching ligands, then click View all to open a dialog that lists all the matching ligands, each shown as a 2D structure with the matched substructure highlighted. You can also click the indicator to open this dialog directly.

Generate Map button

Regenerate (or generate) the map, using the settings in the dialog box.

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