Start the Simmune Modeler. You should see the start page with the version information. The Modeler window has a File Dialog header and a Navigation header. Please select in the File Dialog header: 'Model'->'New'.

Specify a name for the model (e.g. "G_proteins.dbf").

View of the empty model. This page will provide an overview of all molecules, complexes and reactions in the model.

Click on 'Molecule' to open the molecule editing page.

We will start by creating a receptor that has two components, an intracellular and an extracellular component, each with one binding site.

Click 'New' and then 'Add Component'.

Resize the molecule component to make it look like this. Click OK.

With the first component ('Molecule component 1') selected, click 'Add Component' again. Resize it according to the screenshot. Click OK.

You can move the second component to make the molecule look like this.

Add one binding site to each of the two components. First, select the component you want to add a binding site to.

Then click 'Add Binding Site'.

Do the same for the other component. The molecule should then look like this.

Now select the Molecule -- either by clicking on the 'Molecule:...' line in the 'Molecule Composition' tree view or by clicking in the display outside of any of the two components. Set the molecule properties: Type: Protein; select 'Membrane Associated'; Category: Receptor; set Diff_Coeff to 0.001 square microns per second (the diffusion coefficient of a large transmembrane receptor) and specify a name ("Receptor").

Select the Molecule component 1, select as Location 'Inside-membrane', set the name to 'Intracellular Domain' (or something similar).

Select the Molecule component 2, select as Location 'Outside-membrane', set the name to 'Extracellular Domain' (or something similar). These two steps specify that the receptor is inserted into the cellular membrane with component 2 facing the extracellular space and component 1 facing the cytoplasm. Note that this specification of the location of the receptor domains, relative to the membrane, is not just for annotation purposes but will determine which potential binding partners (other molecules) can be seen by the sites of the receptor.

Finally, we assign names to the binding sites of the receptor that will help us identify them when establishing interactions. The binding site of the intracellular domain will interact with the G proteins. Accordingly, we can call it, for example, "G protein recruitment site". The extracellular site will interact with the receptor ligand.

Once, we are done with the molecule, we can click 'Save'. The Modeler application will ask us whether we want to automatically create a single molecule complex species. Please click 'yes'.

After the molecule has been saved and a single molecule complex (which we will work with later) has been created the Modeler will inform you that the model contains items that depend on the molecule (the molecule complex) and that this constrains the possibilities for editing molecule properties. Click 'Clear' or just hit the 'New' button above the molecule list view to work on the next molecule in our model.

The file "G_protein_2.17.dbf" represents the model as it should be at this stage of the tutorial.

Create a second molecule ("Ligand") with properties as shown in the screenshot (eg. size 50X50).

Create a third molecule ("Galpha") with two binding sites, the first site will allow it to interact with the receptor, the second will bind to Gbetagamma. Make sure you specify Galpha to be a membrane-associated molecule and that its only component has as location 'Inside Membrane'. Otherwise the molecule will face the extracellular space after insertion into the cytoplasmic membrane. This property of the molecule can only be set after 'Membrane Associated' has been selected as property for the whole molecule.

Now, we will add a feature to Galpha that will keep track of whether it is in the GTP or the GDP state. To do this, select the (only) molecule component...

Then, click 'Add Feature' and give the feature a name ("GTP").

You can assign a more visible color to the GTP feature by clicking 'Change Color' next to the feature name. Click 'Save' (confirm creation of a single molecule complex) and click 'Clear'.

Create the Gbetagamma subunit with properties as shown in the sceenshot (eg. size 50X50).

Important: Specify that the (only) component has as Location 'Inside-membrane'! Otherwise the molecule will face the extracellular space after insertion into the cytoplasmic membrane. 'Save' and 'Clear'.

The file "G_protein_2.24.dbf" represents the model as it should be at this stage of the tutorial.