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

From OpenWetWare
Jump to navigationJump to search

Practical 1


  • 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
[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