Map Options Dialog Box

Map Options Dialog Box Features

• Ligands to use options
• Map topology type option menu
• Keep existing connections option
• Define custom substructure option menu
  • Use custom core text box and Pick option
  • Extend mapping option
  • Select custom linker text box and Pick option
• Generate Map button

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:

Use custom core text box and Pick option

When defining a custom core, enter one or more SMARTS patterns in the text box, separated by spaces, or select Pick and pick the atoms in the Workspace for the SMARTS pattern of the core. When you pick atoms, a SMARTS pattern is generated for each ligand in the Workspace selection and replaces the contents of the SMARTS text box. You can modify the SMARTS pattern after it is obtained from the Workspace.

When you pick atoms, picking an unselected atom selects it, and picking a selected atom deselects it. You can add multiple atoms to the selection by holding down Shift and dragging over them. The SMARTS pattern in the text box is updated as you pick.

If you change the structure in the Workspace, the current SMARTS pattern is retained, and the Pick option is deselected. Selecting it again clears the SMARTS pattern, ready for picking to define a new SMARTS pattern.

Extend mapping option

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

Select custom linker text box and Pick option

When defining a linker, select Pick and pick the atoms in the Workspace for the SMARTS pattern. The SMARTS text box shows the SMARTS pattern, but it is not editable. The pattern is updated as you pick atoms.

When you pick atoms, picking an unselected atom selects it, and picking a selected atom deselects it. You can add multiple atoms to the selection by holding down Shift and dragging over them. The SMARTS pattern in the text box is updated as you pick.

If you change the structure in the Workspace, the current SMARTS pattern is retained, and the Pick option is deselected. Selecting it again clears the SMARTS pattern, ready for picking to define a new SMARTS pattern.

Generate Map button

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