# 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

• "All models are wrong, but some of them are useful", George Box.
• Possible Explanation: Modelling = Catching the Trend and Explaining it
• Analysis of a problem identifies the most important process shaping the problem
• The effect of each process is described with some equations (or any tools borrowed from mathematics)
• The combination of all the process is simulated.
• Successful modelling = the outcome to simulation is very close to the outcome in real life
• Modelling is therefore wrong (it is an approximation) but useful!

Part II: Getting to know CellDesigner

• Thanks to Dr V rouilly for the Cell Designer Tutorial!!!
• Open a sample file: File -> Open -> Samples/...
• Select items, move them around, delete, undo...

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
$\displaystyle{ A \xrightarrow{k_{1}} B \xrightarrow{k_{2}} C }$
• 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:

\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} }
• 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