Imperial College/Courses/2009/Synthetic Biology/Computer Modelling Practicals/Practical 1

Practical 1

Objectives:

To learn how to use a computational modelling tool for biochemical reaction simulations.
- To build biochemical networks
- To simulate the time evolution of the reactions
To explore the properties of simple biochemical reactions.
Examplar: A --> B --> C model

Part I: Introduction to Computer Modelling

Part II: Getting to know CellDesigner

Read through the tutorial example, and get familiar with CellDesigner features. Official CellDesigner Tutorial
Please Note: the link redirects you to the 2008 tutorials. Make sure that when you are done you come back to this page!!!

Part III: Building Your First Model: A --> B --> C

Now is the time to build your first model from scratch with CellDesigner, and to run a simulation.
The model explored describe a system where a compound 'A' is transformed into a compound 'B', which is consequently transformed into a compound 'C'.
To start, launch the CellDesigner Application: Double Click on the Icon found on your Desktop.
Then follow the instructions below to build the model.

Model	CellDesigner Instructions
[math]\displaystyle{ A \xrightarrow{k_{1}} B \xrightarrow{k_{2}} C }[/math]	Define the topology of the reaction network: Open a NEW document: File -> New. Create 3 compounds A, B, and C (help). Create Reaction_1 linking 'A' to 'B' (help). Create Reaction_2 linking 'B' to 'C' Save your model
Following the Law of Mass action, the dynamic of the system is described as: [math]\displaystyle{ \begin{alignat}{2} \frac{d[A]}{dt} & = - k_{1}[A] \\ \frac{d[B]}{dt} & = k_{1}[A] -k_{2}[B] \\ \frac{d[C]}{dt} & = k_{2}[B] \end{alignat} }[/math]	Edit Reaction_1, Create a NEW local parameter called k1, value equals 1.0 (help). Create a kinetic law for Reaction_1, according to the dynamical system (help). Edit Reaction_2, Create a NEW local parameter called k2, value equals 10.0 Create a kinetic law for Reaction_2, according to the dynamical system. Save your model.
Simulate the dynamical behaviour	Open Simulation Panel (help) In the top left panel set the End Time as 10 seconds Set the number of points as 1000 (gives a nice smooth curve) The panel below will be on the species tab, set Initial quantity of A as 10 Press Execute, and check results.

Part IV: Analysis of A --> B --> C

You are now ready to analyse the behaviour of the biochemical network A --> B --> C.

The following qustions are to be addressed in Section A of your coursework.

First, let us learn a little bit from the simulations:

Plot and Describe the evolution with time of the concentrations of A, B and C, using these default parameters?
Now swap the values of k1 and k2 (k1=10 and k2=1)under the parameters tab
- How does this alter the formation of C?
- How does B change?
- Explain these results

Now, let us place ourselves in the position of an experimentalist.

If you had real life data showing the accumulation of C for an A-B-C reaction you could fit the data using this model and two rate constants would be returned. Could you assign these rate constants to k1 or k2 (yes or no)?
What additional data would you need to assign k1 and k2? (Explain how you would extract k1 and k2)

Part V: Additional Resources

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