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Manage Pharmacophore Hypotheses Panel |
In this panel you can manage the hypotheses that are available to the project. This includes, creating, editing, and deleting hypotheses, importing and exporting hypotheses, and adding excluded volumes to hypotheses.
To open the Manage Pharmacophore Hypotheses panel, you can:
Choose Applications → Phase → Manage Pharmacophore Hypotheses in the main window.
The Manage Pharmacophore Hypotheses panel opens automatically after you create a hypothesis manually—see the New Hypothesis Dialog Box topic for more information.
In the Manage Pharmacophore Hypotheses panel, you can create and edit hypotheses based on an individual structure (the reference ligand), rather than on a set of structures that share common features. This capability allows you to use your knowledge of the binding of a particular ligand to generate a set of pharmacophore features that can be used in a database search.
New hypotheses are created using a set of pharmacophore features. Maestro uses the feature definitions to identify all the possible pharmacophore sites in the reference ligand. You can then choose which sites you want to include in the hypothesis. You can also edit the feature definitions using the Edit Features dialog box.
As well as creating new hypotheses, you can export hypotheses and import them for editing, including hypotheses that were exported from the Develop Common Pharmacophore Hypotheses panel. You cannot edit hypotheses from a pharmacophore model development run directly: you must export them to a file or add them to the Project Table first, then you can edit the copy.
Hypotheses are stored as entries in the Project Table along with their reference ligand. Each hypotheses therefore has an entry ID as well as a hypothesis ID and a title. The Hypotheses table is a restricted view of the content of the Project Table that includes only those entries that have hypotheses.
Warning: When creating a new hypothesis, you should ensure that your structure is a 3D, all-atom structure. If it is not, the pharmacophore features are likely to be incorrectly assigned.
To create a new hypothesis:
Duplicate the entry in the Project Table (Ctrl+D (⌘D)).
This is necessary to ensure that the original entry is not overwritten.
Click New.
Alternatively, you can choose Applications > Phase > Create Hypothesis in the main window.
The Choose Reference Ligand dialog box is displayed. The list in the center of the dialog box lists entries from the Project Table.
Select the duplicated entry from the list.
The entry name appears in the Name text box.
Click Choose.
The New Hypothesis dialog box is displayed. The dialog box has two site lists: one of available sites in the reference ligand, and one of sites selected for the hypothesis, which is initially empty. You can choose which sites are displayed in the Workspace in the Mark sites section. By default, all sites are marked.
Select the sites you want to include in your hypothesis, and click Add.
The selected sites are added to the Hypothesis sites list. You can select multiple sites by shift-clicking and control-clicking. You can also select sites one-at-a-time and add them, and you can remove sites from the list. The Hypothesis sites list does not change when you add or remove sites.
When you have selected the desired sites, click OK.
The New Hypothesis dialog box closes, and the hypothesis is displayed in the Workspace and added to the Available Hypotheses table of the Manage Pharmacophore Hypotheses panel.
To edit an existing hypothesis:
Select the hypothesis in the Hypotheses table, and click Edit.
The Edit Hypothesis dialog box is displayed. This dialog box is identical to the New Hypothesis dialog box. The dialog box has two site lists: one of available sites in the reference ligand, and one of sites included in the hypothesis. You can choose which sites are displayed in the Workspace in the Mark sites section. By default, the hypothesis sites are marked.
Select the ligand sites you want to add to your hypothesis, and click Add.
The selected sites are added to the Hypothesis sites list. You can select multiple sites by shift-clicking and control-clicking.
Select the hypothesis sites you want to remove from your hypothesis, and click Remove.
The selected sites are removed from the Hypothesis sites list. You can select multiple sites by shift-clicking and control-clicking.
When you have made the desired changes, click OK.
The Edit Hypothesis dialog box closes.
The toolbar contains four buttons:
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View Hypothesis Labels Displays feature labels for the selected hypothesis in the Workspace. |
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View Excluded Volumes Displays excluded volumes for the hypothesis in the Workspace. |
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View Site Measurements Display markers for the distances and angles in the selected hypothesis. Opens the View Site Measurements panel, in which you can select the distances and angles to be displayed. |
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View Matching Tolerances Displays feature-matching tolerances for the features in the hypothesis as a set of spheres whose radius is the tolerance. The spheres are colored the same as the features, but are semi-transparent. |
The Hypotheses table lists the hypotheses that are in the Project Table. You can select a single row of the table, for editing, deleting, adding excluded volumes to, or exporting the hypothesis. The columns of the table are described below. The table is noneditable, with the exception of the Title and the Hypothesis ID. As in the Project Table, the In and Title columns are in a fixed region, and the remaining columns are in a scrolling region.
| In | Inclusion status of the reference ligand and its hypothesis data. The diamond has a cross in it if the ligand is included in the Workspace, and is empty if the ligand is excluded. You can include and exclude ligands and their hypotheses with click, shift-click and control-click. The hypothesis features are displayed as described in the Create Sites topic, and are labeled by the feature letter and index. The index used here is an index of the features in the hypothesis. | |
| Title | The title of the project entry for the hypothesis. You can edit this column to change the title. | |
| Hypothesis ID | The identifier of the hypothesis. For new hypotheses, the identifier is constructed automatically from the feature letters and the entry name of the reference ligand. For hypotheses that were imported or added to the Project Table from a pharmacophore model development run, the identifier is the identifier from the run. | |
| Entry ID | The project entry ID. | |
| Entry Name | The project entry name. | |
| Phase Activity | The activity used in pharmacophore model development | |
| QSAR | Indicates whether a hypothesis has an associated QSAR model. | |
| Excluded Volumes | Indicates whether a hypothesis has associated excluded volumes. | |
| Phase Run Name | The name of the run from which the hypothesis originated. For hypotheses created directly from a reference ligand, this is a series of dashes. | |
| Hypothesis Date | The date that the hypothesis was last modified. | |
| # Sites | The number of sites in the hypothesis. |
The buttons below the Hypotheses table allow you to perform various actions on the selected hypothesis, or to add hypotheses to the table.
Create a new hypothesis. Opens the Choose Reference Ligand dialog box, then the New Hypothesis dialog box.
Edit the selected hypothesis. Opens the Edit Hypothesis dialog box.
Delete the selected hypothesis from the table and from the project. Hypotheses that were imported or obtained from a run are not removed from their original locations, so they can be reimported.
Import a hypothesis from disk. Opens the Import Hypothesis dialog box, in which you can navigate to the desired hypothesis.
Export the selected hypotheses to disk. Opens the Export Hypothesis dialog box, in which you can navigate to a location to save the hypotheses.
Add excluded volumes to the selected hypothesis. Opens the Excluded Volumes dialog box.
Set up site-specific tolerances and matching criteria. Opens the Matching Conditions dialog box.
Open the Advanced Pharmacophore Screening panel with the selected hypothesis loaded. This button is not active unless a single hypothesis is selected in the table.
When you right-click and hold in a row in the Hypotheses table (or on the H button in the Project Table), a menu is displayed, containing various actions you can perform on the hypothesis.
Opens a submenu from which you can choose what to display:
The reference ligand is displayed and undisplayed by the normal Maestro mechanism, so you can display and undisplay the reference ligand independently of this menu.
Choose a color scheme for the hypothesis and the reference ligand.
View properties of the hypothesis in the Workspace. Opens a submenu, from which you can choose from the following items:
These items perform the same task as the corresponding toolbar buttons.
Align the selected hypotheses to a reference hypothesis. Opens the Align Hypotheses dialog box, in which you can set up and perform the alignment.
Export the selected hypotheses to files. Performs the same function as the Export button.
Open the Advanced Pharmacophore Screening panel. The hypothesis you clicked on is selected as the hypothesis to match.
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