and HearDock 
and HearDock The program DOCK postulates binding orientations, given structures of the "ligand" and "receptor" molecules. It is often of interest to use the structure of a molecule that is important in physiology or disease to find other molecules to bind it and modulate (usually inhibit) its function. Generally, one searches a large database of commercially available compounds with DOCK, treating each as a possible "ligand," against the structure of a target protein, treated as the "receptor." Simple scoring methods are used to identify the most favorable binding modes of a given molecule, and then to rank the molecules according to these best orientations. The output consists of a large number of candidate ligands in the binding orientations considered most favorable by DOCK. It is then up to human users to look through the molecules and decide which ones are worth pursuing in the real (as opposed to the virtual) world. It is beyond the scope of this manual to describe DOCK in further detail; please consult the DOCK web page and other information from Kuntz and coworkers, who have created and developed the method over the last several years.
ViewDock facilitates the selection of compounds by a human user from the output of DOCK version 4. For a less formal explanation of the program, see the ViewDock tutorial. With a single mouseclick, the user can view an individual docked molecule and simultaneously display its name, DOCK scores, and other information. The list of molecules can be sorted in various ways, edited to remove compounds deemed uninteresting, and saved for future reference. HearDock includes the functionality of ViewDock, but also allows sounds to be associated with properties such as score.
There are several ways to start ViewDock (or HearDock), a tool in the Docking category. Explicitly starting ViewDock (or HearDock) brings up a dialog requesting the file of molecule orientations previously output by DOCK 4. When the file containing the docked molecules in either Mol2 or PDB format has been read, the ViewDock ListBox will appear and all of the molecules will be displayed in the main Chimera window. ListBox menu items are explained within the following sections, and a full listing with short descriptions is included at the end of this page.
Most users will want to view the molecules individually in the context of the receptor site, and thus will open the structure of the receptor molecule, display and color the portions of interest, and change representations or include surfaces as desired. Coloring atoms by type may also be helpful. Once the appropriate viewing context has been set up, individual docked molecules can be examined using the graphics window and ListBox.
| ViewDock ListBox |
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At first, all of the lines in the upper panel of the box are highlighted; the lower panel is blank, since more than one molecule is chosen in the upper panel. Clicking on a line in the top panel chooses the corresponding molecule and causes information about that molecule to be shown in the lower panel. The chosen line is highlighted, and in the main graphics window, only the docked molecule that has been chosen is displayed. By default, the upper panel shows molecule status (more on this below), sequence number (by order of occurrence in the DOCK output file), and name. The lower panel shows more detailed information on the chosen molecule, including sequence number, source number (by order of occurrence in the database file input to DOCK), name, description, and scores. Any of these descriptors can be included in or removed from the listing in the upper panel using the Column... Add and Delete options. The listing can be sorted by any one of the descriptors (Sort).
If the ListBox becomes obscured by other windows, it can be resurrected using the Raise option for the ViewDock instance in the Tools menu. There is also a Quit option, which has the same effect as File... Exit.
The user can click through and edit the list of compounds. Three mutually exclusive states are possible for each compound: viable, deleted, or purged. The initial state is viable, but if the molecule is deemed uninteresting, it can be changed to deleted or purged by clicking on the checkboxes near the bottom of the ListBox. Individual compounds or blocks of compounds can be chosen (highlighted) with the left mouse button within the ListBox upper panel. Ctrl-click adds to an existing choice rather than replacing it. To highlight a block of compounds without having to hold down the mouse button, click on the first (or last) and then Shift-click on the last (or first) in the desired block. Clicking a status checkbox will then change the status of the entire set.
In general, viable compounds are interesting (or have not been looked at yet), deleted compounds are less interesting but may deserve another look, and purged compounds are meant to be discarded. When structures are written out using File... Rewrite, viable and deleted but not purged structures are included in the output file. In contrast, structures in all three states are included in a file written out using File... Save or File... Save As. The states of the molecules are also recorded in these output files, which can be input to later sessions of ViewDock (or HearDock). The ListBox menu options control which status groups appear in the upper panel.
There are other ways to change status besides clicking a status checkbox. If Selection... Prune is activated and part of a compound is picked in the graphics window, the compound is undisplayed and marked as deleted. Chimera... Hydrogen Bonds uses hydrogen bonding information computed by FindHBond to filter the compounds and change their status based on number of hydrogen bonds to the receptor or a selected portion of the the receptor. Additional tips for filtering by H-bonds:
Individual compounds are submodels of a single model (model 0, for example) and are specified #0.1, #0.2, etc. (see atom specification syntax). Even though they are termed submodels, the display of each compound can be independently disabled or enabled at the model level (see display hierarchy). Within ViewDock, there are two ways to control model-level display:
For example, if only the first five compounds are display-enabled,
Command: ~disp #0.2will work. In contrast, other commands like
and
Command: disp #0.2
but not
Command: disp #0.8
Command: label #0.7are executed, although their effects may not be visible until the corresponding molecules are displayed. After the following,
and
Command: color pink #0.6
Command: ~disp #0only the compounds whose display is enabled at the model level will be displayed.
Command: disp #0
Note that DOCK 4 interprets information about each molecule as Name or Description based on where this information occurs in the input database file. Here are examples of a single molecule from (A) a Mol2 database file input to DOCK 4, (B) a Mol2 output file from DOCK 4, and (C) a PDB output file from DOCK 4. Remember that ViewDock and HearDock accept either format of DOCK output. The multiple molecule files are simply concatenations of the data for single molecules. Number is sequential number in order of occurrence in the DOCK 4 output file, and Source num is the sequential number in order of occurrence in the database file input to DOCK.