Step 2
Quantify Your Hypothesis
Shortcut: Right click your model in the database pane and select "Run Initial Simulation." You will be asked a few questions and then your model will be solved for a prototype experiment. Then you can skip to Step 3.
To begin step 2, right-click the model you want to quantify on the Models tab in the database pane. Select “Create Model Realization”. A model realization (sometimes called a quantitative model) is a version of your diagram that can be solved computationally. A given model may have many model realizations. This is because you might have several ideas about how best to write the rate law for a given process and you might want different model realizations with different initial values for your states. You also might want to impose different sets of constraints in different model realizations.
We often use MR as an abbreviation for Model Realization.
We’ll illustrate the process of creating and completing an MR using the cAMP model developed in Step 1. scroll or use the search box to find “new model for Help System” on the Models tab of the database pane. Right click and select Create Model Realization.
ProcessDB will then automatically create an MR for this model. This can take a few seconds for large models because default rate laws are being written for every process in the model based on the mass action principle from chemical kinetics.
When your MR has been created it is automatically added as a branch in the model tree structure in the database pane as shown below. The new MR will be assigned a unique identifier which is visible to the right of the MR name. Click the save icon (
) to save the MR to the database.
You will see a unique ID for this MR:
The new MR's diagram will display in the diagram pane.
Tip: You can always tell when you are looking at a MR diagram because MRs are always displayed on a violet-blue background.
Notice that except for the violet-blue background the MR diagram is identical to its parent model diagram. But on this screen you can access the mathematical and numerical details of your model. Right click on the process named cAMP secretion and select Model Realization Properties. This opens a dialog box where you can view, edit or delete the rate law for this process. You can also add a new rate law of your own design.
The dialog box displays the current rate law for the selected process. The left hand side of this equation is the default symbol for the flux of molecules through this process. A default process symbol is the letter P followed by the numerical process ID. The right hand side of the current rate law equation is an algebraic expression that gives the flux of molecules as a function of the States with roles in this process. In this case, for example, the rate law is
P2828 = kP2828_1 * S4955.
Here, S4955 is the default symbol for the state, cAMP in cytoplasm, which is the START or reactant for the process of cAMP secretion. kP2828_1 is the rate constant governing the speed of this reaction. ProcessDB recognizes reactions that are first or second order and automatically supplies an initial value for the rate constant. This choice must assume a set of consistent units and the ProcessDB default units for states are abundance units (molecules per cell). First order rate constants are set to 0.1 s-1 if the user’s times are expressed in seconds or 0.1 min-1 if the user is working in minutes. The topic of choosing a model’s units could be a course of its own. There is more information on choosing units here (coming soon).
Notice that the field containing the current rate law is a drop-down list. If other rate laws have been proposed for this process, any of the alternate rate laws can be made the current rate law by selecting it from the list.
The current rate law can be edited by clicking the Edit button, or deleted by clicking the Delete button.
If you wish to supply your own rate law for this process, click the Add button above the current rate law in the row labeled Process Rate Law Controls.
With the Properties dialog box still open you can select other processes on the MR diagram and see their rate laws. Notice, for example, that the default rate law written for cAMP receptor binding is a second order rate law and the corresponding second order rate constant is 1E-6 or 0.000001, again assuming units of abundance (molecules per cell). This second order rate law was written automatically by ProcessDB based on the states and roles included in the diagram of this process. Similarly, if you select the process, cAMP phosphodiesterase, you will see that ProcessDB recognizes this as a single substrate enzyme catalyzed reaction, again based on states and roles, and writes the corresponding Michaelis-Menten rate law automatically.
Still with the Properties dialog open, click on a state in the MR diagram, say, cAMP in extracellular space. In this way you can see and edit the symbol used for this state, its initial numerical value and whether or not this state is on the Boundary of the model. You can also change the shape associated with any state and the background color of this shape. Many ProcessDB models are beautiful. Try out these controls and see if they help you convey information.
Finally, with the Properties dialog still open, click on the background of your MR diagram – anywhere except a process name or a state name. This will display MR properties that are not specific to any given state or process.
Values for all of the model parameters are displayed. These may be edited in place or deleted, and new parameters can be added to the MR by clicking the Add button on the Model Realization Parameters tool bar.
Model Realization Functions can also be defined in this dialog. ProcessDB includes this feature so that you can include several frequently used model features:
- Rate constant constraints
- Useful functions of the model variables to be displayed in plots or tables
- Functions representing diagnostic figures of merit
- Functions you want to calculate and perhaps re-use in other functions or rate laws
- Any function useful to you
To add a new MR Function, click the + button at the bottom of the list of Model Realization functions. This opens the Create MR Function dialog that makes it easy to select states and processes from your model for use in your equations without re-typing. Any state or process can be double clicked to insert it at the cursor in your new MR function.
You are now ready to define your experiments in Step 3 of the modeling process.