SimBiology®

Building a Model for the Mutant Strain

Modeling the Mutant Strain

The deletion in SST2 results in uncatalyzed G protein deactivation (Reaction 6; Ga -> Gd). From a modeling perspective, this means a change in the rate of the reaction. This section shows you how to copy the previously built model into a new model session, change the parameter value to reflect the change in the rate of the reaction, and simulate the new model.

An another method to apply alternate values in the model is by using Variants. See Variants in the SimBiology^® Getting Started Guide. For more information about using variants in this example see Applying Alternate Values Using Variants.

Note   An additional simplifying assumption of this model is that there are no changes in the initial amounts of species or the rate of any other reaction.

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Copying a Model

To copy a model, you first need to save the model to be copied as a SimBiology project. If you have not yet done so, see Saving Your Work as a SimBiology^® Project File.

Use the following procedure to import a model created in your SimBiology project. This is a convenient way to "copy" a model in the project and change the copied model while preserving the previous version.

1. From the File menu, select Import Project Contents.

   The Open SimBiology Project dialog box opens.

2. Browse to and select the project.

   yeast_g_protein_cycle.sbproj

3. Click Open. The imported model opens in a new model session.

This section showed you how to copy a model into a separate model session and change a component value to represent, for example a mutant phenotype. The complete example uses this method to illustrate the work flow.

The next section shows you an another method to apply alternate values to model components through variants. You can also try the same work flow using the variant. To skip the next section and continue with the example see Changing Model Settings.

Applying Alternate Values Using Variants

If you want to use a variant to apply the change in parameter value:

1. In the Project Explorer, expand Model Variable Settings (for the wild-type model), and double-click Variants to open the Variants pane.

2. In the Enter Name box, type a name for the variant, and then click Add or press Enter. For example:

     mut_value

3. Add content to the variant:

   1. In the Settings tab, click Add. The table updates with a row containing information about a model component.

   2. From the Type list, select parameter.

      The Property list updates to show the property available for storing.

   3. In the Name cell, type the name of the component.

      Gprotein Inactivation.kGd

      The parameter kGd is at the kinetic law level, and not the model level. Thus, you must specify the parameter in the format ReactionName.ParameterName.

   4. In the Value cell, type a value to apply using the variant.

      0.004

If you want to use the variant for the rest of this example, you must select the variant during simulation, to represent the mutant phenotype.

To apply the variant during simulation:

1. In the Project Explorer, double-click the Simulation task, to open the Simulation pane.

2. In the Variants table, select the Use In Task check box for mut_value.

3. Click (Run).

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Changing Model Settings

The copied model has the simulation settings used for the previous model. Therefore, the only settings to change are the name of the model and the value of the parameter kGd. Remember to select the appropriate items in the newly created model session.

1. Rename the model. In the Project Explorer, double-click SimBiology Model to open the SimBiology Model.

2. Click the Settings tab.

3. In the Model Name box, enter the following:

     Yeast_G_Protein_mut

4. Locate the parameter kGd for the Yeast_G_Protein_mut using Find in the top-right corner of the SimBiology desktop.

   1. In the Find box, enter kGd and press Enter. The Output pane opens with the results of the search.

   2. Locate the parameter kGd for the mutant strain. Note that the results are organized by model and the model components are listed.

   3. Double-click the row containing the parameter kGd under the model Yeast_G_Protein_mut. The desktop opens the Parameters pane with the row containing kGd selected.

   4. Change the value of kGd from 0.11 to 0.004.

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Simulating the G Protein Cycle Model

Simulating the G Protein Cycle Model of the Mutant Strain