1. CellDesigner and Virtual Cell Leang Chhun and Chanchala Kaddi Georgia Institute of Technology 29 June, 2006

2. Goal Describe two simulation tools –CellDesigner and Virtual Cell Brief tutorials of each –Separate case study

3. CellDesigner Free download; no registration required SBML compliant –standardized technology Can be run on multiple platforms –Windows –MacOS X –Linux –FreeBSD Graphical Notation, Mathematical Notation www.celldesigner.org

4. Case Study Belousov-Zhabotinsky (BZ) Reaction –Oscillating reaction –Does not follow equilibrium thermodynamic behavior –Traces concentrations BrO 3 HOBr Cerium(IV) Br HBrO 2

5. Steps to Complete Model Create the physical model Add other information –Reaction equations –Reaction rates –Parameters Simulate model Analyze results

6. Layout Component Icons Physical Model Parameters

7. Creating the Model Compartments Species Reaction arrows

8. Physical Model CellDesigner Model of Belousov-Zhabotinsky Reaction Compartment Species Reaction Arrows

9. Add Information Reaction equations –Concentration of species –Rate constants Initial parameters

10. Parameters Definitions of species, reactions, etc. Initial values of species Reaction equations Reaction rate constants

11. Simulation/Results Simulation>Control Panel Define end time and number of points Execute Directly plotted

12. Control Panel End time, # of points Parameter values Output Plot

13. Results CellDesigner results of BZ Reaction (Run time: 1000s, # of steps: 100 Oscillation patterns

14. CellDesigner Summary Models biochemical networks –GUI –SBML Graphical and mathematical notation Select different species types SBML ODE solver

15. Virtual Cell Free but must be registered user Can only be run from website Run as Java Applet or Java Application –Requires Java Runtime Environment 3 components: –Modeling framework –Mathematics framework –Internet based www.vcell.org

16. Case Study Online tutorials Used to show capabilities of software Models calcium channels and pumps through membranes Facilitated calcium diffusion in epithelial cells http://www.vcell.org/login/facil_ca_dif.pdf

17. Creating the Model Add compartments/membranes –Select feature tool and label membrane and compartment Add species –Defined in parts of compartments

18. Physical Model Biomodel of Facilitated Calcium Diffusion Pointer Membrane Species

19. Add Information Reaction equations (case specific) –Add flux across membranes –Add flux equation to flux icon Initial parameters Virtual Cell Flux diagram

20. Add Application Case specific –Add geometry associated with case study

21. Simulation Application window>Simulations Run Results saved to online database View results Time Scroll Geometry (Cell) Species

22. Virtual Cell Change in concentration of CaB 1sec 5sec 3sec 10sec

23. Virtual Cell Summary Models biochemical networks; java interface Graphical and mathematical interfaces. General species, features tools. Several ODE solvers

24. Comparison CellDesigner Virtual Cell Ease of Use: No tutorials Several tutorials Simulations: GUIs; SBML, No SBML SBW Databases: Biomodels.net KEGG

25. Comparison CellDesigner Virtual Cell Geometries: N/A 2D & 3D Electrical: N/A Membrane Mapping Potentials, Stimuli ODE Solvers: SBML ODE Euler, Runge- Kutta, etc.

26. Drawbacks CellDesigner –Concentration plots only –Only one ODE solver Virtual Cell –Internet connection required –Not SBML based

27. Positive Features CellDesigner –Concentration plots –GUI, graphical notation –SBML compliant Virtual Cell –3D visual aid –Electrical mapping –Multiple ODE solvers