View Hypothesis Workbench

Using a Template Molecule to Place Functions in a Hypothesis

You can use a template molecule to construct a hypothesis that represents the chemical functionality of a particular compound. For example, suppose that you want to build a hypothesis that has three hydrogen bond acceptors in specific locations relative to each other. If you know of a compound that has three hydrogen bond acceptors in the same relative locations as in you need in your hypothesis, you can use the compound as a template. A template compound can identify the locations of the hydrogen bond acceptors or other functions for placing the desired hypothesis functions. The below shows an example of how a particular compound was used to locate functions to create a hypothesis that represents some of the compound's chemical functionality.

Building a Hypothesis with a Template Molecule

Please Note: The order of operations is very important when building a hypothesis from a template molecule. The location constraints or weights must be added before the individual features are merged together. See explanation below.

Find a conformer of a molecule that has chemical functions in the relative locations that you want. You can use the first few steps in this procedure to check whether a particular molecule has the functions that you need.
Bring a candidate template molecule into the View Hypothesis workbench. Any conformer that has the needed functions in the proper relative locations can be used as a template.
To obtain the molecule, you can use the View Compound workbench or the View Compound QuickTool to build it, use the Find... command in the Data menu or search a database to find an appropriate compound in a database, or import a molecule.
Display the candidate molecule in the View Hypothesis workspace.
If you want to look at several conformers to use as the template, and a conformational model has not been generated, generate conformers first. See the section on Conformer Generation.
To search for and display in the workspace a conformer with the right function locations, use the Show Conformers... command of the Tools menu, as discussed in To Display, Delete, Register, and Unregister Individual Conformers. To bring a likely candidate conformer to the workspace, use the AddToView button in the Show Conformers dialog box.
Select from the Feature Dictionary a function that you want to include in your hypothesis. For example, if you want to find the features in your template molecule that you can use to place hydrogen bond donors, select HB DONOR.
From the Style menu select the Wireframe command. (Some of the mapped functions are only visible when the molecule is displayed in Wireframe style.)
Left-click on any component in the template molecule to select it.
From the Tools menu, select Show Function Mapping.
If the molecule contains any instances of a selected vector function, such as HB DONOR or HB ACCEPTOR, a blue arrow with a magenta sphere at the head appears, mapping the position of one of those instances, except the HB Acceptor (lipid) is displayed as a green and white cone.
See the example below.
If the feature selected is a point feature, such as a hydrophobic or negative charge, a magenta sphere appears, marking the currently mapped position of one of those instances.

The Status area displays the message: "Mapping 1/n", where 1 indicates it is the first instance of that type of function, and n is the total number of instances of the selected function that the molecule contains. For example, if you selected HB DONOR in the Feature Dictionary, and the molecule has three potential hydrogen bond donors, then n equals 3.
If the molecule does not contain any instances of the selected function, the Status area reports "No mapping."
Also displayed is the Function Mapping dialog box, allowing you to step through the different instances of the selected function in the molecule, and add the ones you want to your hypothesis (lower right of previous page graphic).
To see additional instances of the function, click on the forward display button.

The sphere or vector mapping indicator moves to the next instance of the selected function in the molecule, if there is another one. The status area reports "Mapping 2/n".
Each time you click on the forward display button, the next instance of the selected function in the molecule becomes the currently mapped position. When the indicator has mapped the last instance of the function, clicking on the button again does not change the display.
You can left-click on the reverse display button
to step back through all of the instances to the first one.
To check the relative locations or distances between functions, use the Measure tool in the Toolbox.
When the currently mapped function appears in the location (and for vector functions, the orientation) that you want, left click on the Add Function button in the dialog box.
The function is fixed in the currently mapped position. The magenta mapping indicator disappears and the function is displayed selected and highlighted. The feature is now a one-feature hypothesis that is not connected to the template molecule.
You can continue to step forward or backward through the instances of the selected function on the template, and when a function you want in your hypothesis is mapped, left click on the Add Function button to add more functions to the workspace.
Each function added in this manner has the same 3D coordinates as the position to which it is mapped in the template molecule. Each newly added function is a separate one-feature hypothesis.
Note: Do not do any rotating or moving unless all of the functions are selected, or you will lose the relative locations of the functions.
To add a different type of function to your hypothesis, make sure that a component of the template molecule is selected (not an added function), then select the new function you want to map from the Feature Dictionary. For example, you may want to add a negative charge function. Select NEG CHARGE from the Feature Dictionary, and then Show Function Mapping from the Tools menu.
Repeat the procedure of stepping through the mapped instances of the function, and using the Add Function button for instances you want in your hypothesis.
When all functions needed have been added to the template, click on the Cancel button in the Function Mapping dialog box. The dialog box and any current mapping display disappear.
In the workspace you now have a template molecule and several separate functions (independent hypotheses) in the correct relative locations and orientations.
VERY IMPORTANT NOTE: If you want to merge the functions into one hypothesis, but have them remain distinct features with different weights, YOU MUST set weights and/or location constraints for each function before merging them together. See "To Set Feature Weights" for a description of setting weights. WARNING: If the merge is performed before the location constraints are added, the user will see very strange results (such as long search times or a negative fit value between a molecule and the hypothesis)!
Or see "To Add Location Constraints" for location constraint information.
To merge the functions together into a single hypothesis, continue to the next topic.

To Merge Separate Functions into One Hypothesis

After you have used a template molecule to place functions in the workspace of the View Hypothesis workbench, and have set weights and/or location constraints for those you want to be separate features (see previous section), you can merge the functions into one hypothesis, as follows:

Select all the functions you want to be included by using the extend select technique (middle mouse button) or by region selection.
Select the Merge Features tool in the Toolbox.

The workspace now shows the template molecule and a single hypothesis that consists of the merged functions. You can rotate and move the hypothesis as a single object.
Select the hypothesis and then save it using the Save To Lab As command from the Data menu. In the dialog box that appears, make sure that the hypothesis is displayed, and not the template molecule.
After you have saved the hypothesis, clear the workspace by selecting the Clear Display command from the Edit menu.
You can now drop the hypothesis back into the workspace to continue editing it if desired.
You can add location constraints to any of the existing functions. However, if you add more items to the hypothesis, for example by adding fragments from the Feature Dictionary, you should not add location constraints to them, for the reasons discussed in The Theory of Building Hypotheses that Have Location Constraints.

For more information on modifying your hypothesis, choose from:

To Merge Functions and Topology into One Hypothesis

To Build a Hypothesis Consisting of Functions and Topology

After you have used a template molecule to place functions in a hypothesis, you can convert the parts of the template molecule to a topology feature and merge it with the functions as follows:

Place the functions on the template molecule as described previously.
Edit the template molecule appropriately. In general, you do not want to have fragments in your hypothesis that is already represented by a function. For example, if you have placed a hydrogen bond donor function at the location of a nitrogen atom, you do not want a nitrogen atom specification also in your hypothesis in the same location, since the hypothesis then will specify both the atom and the HB Donor in the same location, and no molecule will match it.
Before you merge the functions together, left click on the template molecule to select it. Be very careful not to move the molecule when you click on it.
Select the Convert Molecule to Hypothesis button in the Toolbox.

The molecule becomes a hypothesis.
For any separate objects that you want to remain separate features after merging, set weights and/or location constraints for them before the merge.
In the workspace, select all the components that you want to merge together into the hypothesis.
Select the Merge Fragments/Functions command in the Tools menu.
Everything in the workspace is now part of the same hypothesis.
In the hypothesis the locations of the functions are exactly the same as in the original template molecule.
You can continue editing the hypothesis if desired, and then save it to the shelf.
You can add location constraints to the atom specifications or functions in your hypothesis to provide an allowed tolerance on their location relative to the other features, or you can add distance constraints between features that do not have location constraints. For more information about location constraints, see Building Hypotheses that Have Location Constraints.

For more information on modifying your hypothesis, choose from:

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Last updated April 17, 1996 at 08:04pm PDT.