Edit Features Dialog Box

The Edit Features dialog box allows you to change the content of pharmacophore features. Features are defined in terms of SMARTS patterns. You can add patterns to both built-in features and up to three custom features. You can edit and delete custom patterns, and you can exclude or ignore both built-in and custom patterns in a feature.

To open this dialog box, click Edit Features in the Hypothesis Settings Dialog Box.

  • Using
  • Features
  • Additional Resources

Using the Edit Features Dialog Box

Loading Feature Sets

The built-in feature sets are stored with the distribution. You can reload them by clicking Reset All. This button also clears the custom sets.

You can import a feature set from a file by clicking Import from File, and navigating to the feature file. Feature sets can be saved to a file by clicking Export, and specifying the file location in the file selector that is displayed.

You can import a feature set from a hypothesis in the project by clicking Import from Entry, and selecting the desired project entry in the dialog box that is displayed.

The patterns that define a feature set are displayed in the Pattern list table when you choose the feature from the Feature option menu.

Adding Custom Features

Phase supplies six built-in features. You can augment these features with new patterns but you cannot delete them. If these features do not meet your requirements, you can create up to three custom features. These features have the one-letter code X, Y, or Z. To create a custom feature, click Add Custom Feature. A dialog box opens, in which you can name the feature. When you click OK, the feature is added to the feature menu and selected, so that you can add SMARTS patterns to define the feature.

Using Projected Points

By default, donors and acceptors are represented by vectors originating at the donor (hydrogen) or acceptor atom. The alignment of these vectors is used to determine whether ligands share the associated feature. Sometimes, two active ligands can form a hydrogen bond to the same receptor site, but from different directions. With the default representation, these two ligands would not contribute to the same pharmacophore hypothesis.

You can replace the vectors with points at a specified distance from the ligand donor or acceptor atom. These points simulate the corresponding acceptor or donor in the receptor, and are called projected points. To use projected points, select Projected points only. To use the same distance for all patterns, enter a distance in angstroms in the Distance text box, and click Set Distances. To set a distance for an individual pattern, edit the value in the Distance column of the Pattern list table for the pattern.

When you select Projected points only, only the patterns that have a vector geometry and a defined projected point type contribute to the feature. All other patterns that are not excluded are ignored. Vector alignments are not used because the vectors have been replaced by points.

Adding and Editing Custom Patterns

If the patterns in a given feature do not cover all the functional groups that you want to include in the feature, you can add extra patterns. To add a new SMARTS pattern, click New. In the New Pattern dialog box, you can enter a SMARTS pattern and choose the geometry - whether it represents a group, such as an aromatic ring, a single point, such as an atom, or a vector, such as a hydrogen bond acceptor or donor - and the projected point type - whether it has a direction or orientation associated with it, such as aromatic ring orientation or lone-pair direction. Once you have added a custom pattern, you can edit it with the Edit button or delete it with the Delete button.

If the SMARTS pattern you want to add is similar to an existing pattern, you can select the pattern, then right-click and choose Duplicate Pattern from the shortcut menu. The pattern is duplicated as a new custom pattern. You can then click Edit to edit the pattern. The Edit Pattern dialog box has the same features as the New Pattern dialog box.

Setting the Status of Patterns

Matching of patterns to ligand structures is done in the order specified in the Pattern list table. If you have added custom patterns, you can move them up and down the list with the arrow buttons below the list, to set their priority. You cannot change the order of the built-in patterns.

If you want to exclude functional groups represented by a pattern from the feature, you can select the check box in the Exclude column for the pattern. For example, you might want to exclude a carboxylic acid group from being considered as a hydrogen bond donor, because it will be ionized under physiological conditions.

If you want a pattern to be ignored, you can select the check box in the Ignore column. Ignored patterns are equivalent to deleted patterns. If you want to save a custom pattern for later use, but not use it in the current feature, select the check box in the Ignore column.

Visualizing Patterns

If you want to see a patterns for a given ligand or group of ligands, you can display the ligands in the Workspace from the Entry List, and select the check box in the Mark column (of the Edit Features dialog box) for the pattern in the pattern list. Any occurrences of the pattern are marked in the ligand structures.

You can display markers for more than one pattern, but the markers do not distinguish between patterns.

Edit Features Dialog Box Features

Feature set buttons

These buttons allow you to load and store feature sets.

Import From Entry

Opens a dialog box in which you can select a hypothesis entry in the project from which to import features.

Import From File

Opens a file selector in which you can browse for feature files (.def).

Export

Opens a file selector in which you can browse to a location to write a feature file (.def).

Reset All

Reloads the default, built-in features. Custom features are also removed.

Feature Controls

These controls allow you to modify feature content and how they are handled.

Feature option menu

Select an existing feature for editing. The patterns that define the feature are listed in the Pattern list table.

Add Custom Feature button

Opens the Add Custom Feature dialog box, in which you can specify a name and choose a code letter for the new custom feature. The custom feature is added to the Feature option menu and the Pattern list table is cleared.

Delete Custom Feature button

Deletes the current custom feature.

Projected points only option

When selected, patterns with vector geometry and a defined projected point type are represented by a point placed along each vector at a specified distance from the vector atom. This representation simulates the corresponding features in the receptor. All other patterns are ignored. Because the vectors are converted into points, vector alignments are not checked or scored.

Distance text box

Specify the distance from the vector atom to place the projected point for all patterns in the feature. You must click Set Distances to apply the value. Only enabled when Projected point only is selected.

Set Distances button

Set the distance of the projected point to the vector atom to the value in the Distance text box for all patterns in the feature. Only enabled when Projected point only is selected.

Pattern list table

The Pattern list table lists all the patterns that are used to define the pharmacophore feature. You can only select one row at a time in the table, and the text fields are not editable. The shortcut menu allows you to duplicate a pattern as a new custom pattern. The new pattern becomes the selected table row.

The table columns are described below.

Mark   Column of check boxes. Selecting a check box marks the pattern on any ligands that are displayed in the Workspace.
Pattern   Pattern definition. With the exception of default hydrophobic features and aromatic rings, the definitions are all SMARTS strings.
Geometry   Designates physical characteristics of site. Can be one of group (defined by a group of atoms), point (defined by a single atom), or vector (defined by an atom and one or more directions).
Projected Point Type   Defines the directionality of vector features. Can be an aromatic ring, a donor, an acceptor with one or more lone pairs, or none (non-vector feature).
Atom Numbers   The list of atoms that determine the location of the site, numbered according to the SMARTS string. Point and vector geometries use a single atom, whereas group geometry uses multiple atoms.
Distance   Distance of the projected point from the ligand atom. This column only applies when Projected points only is selected. To change the distance for a pattern, you can edit the value in this column.
Exclude   Column of check boxes. Selecting a check box excludes the atoms in this definition from being mapped by other definitions. This is essentially a NOT operator.
Ignore   Column of check boxes. Selecting a check box ignores the pattern when searching for features. Equivalent to deleting the pattern, but keeps the pattern in the table.
Workspace   Indicates whether the SMARTS pattern is present in the structures in the Workspace.
Ligands   Indicates whether the SMARTS pattern is present in the ligand set.

Custom Pattern Editing Buttons

New button

Opens the New Pattern Dialog Box, in which you can enter a SMARTS pattern and choose how it is used to define a site point.

Edit button

Opens the Edit Pattern Dialog Box, in which you can edit an existing custom pattern. This button is not available until you select a custom pattern in the Pattern list table.

Delete button

Deletes the selected custom pattern. This button is not available until you select a custom pattern in the Pattern list table.

Up and down buttons

The up and down (arrow) buttons move the selected custom pattern up and down the table. You can move the custom patterns in among the built-in patterns, but you cannot move the built-in patterns.

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