Model to simulate

This is a modification of the widely cited Goldbeter (1991) minimal (3-variable) model for a mitotic oscillator. The three variables represent Cyclin ( C), inactive cdc-2 Kinase (M), and an active cdc-2 Kinase (X). Two additional variables Y, Z control the dynamics of the inhibitor.

Reference:

Gardner TS, Dolnik M, Collins JJ. A theory for controlling cell cycle dynamics using a reversibly binding inhibitor. PNAS 95: 14190-14195 (1998).

Model file (CellDesigner 2.0) to download

Simulation Step by Step

1. Set the value and formulas

1. "Species" list: Set the initial value
   

   type

   positionTo Compartment

   id

   name

   compartment

   quantity type

   initial Quantity

   substance Units

   spatial SizeUnits

   hasOnly SubstanceUnits

   b.c.

   charge

   constants

   UNKNOWN

   inside

   EmptySet

   EmptySet

   cytoplasm

   Amount

   0

   FALSE

   TRUE

   0

   FALSE

   UNKNOWN

   inside

   C

   C

   cytoplasm

   Amount

   0

   FALSE

   FALSE

   0

   FALSE

   UNKNOWN

   inside

   M

   M

   cytoplasm

   Amount

   0

   FALSE

   FALSE

   0

   FALSE

   UNKNOWN

   inside

   X

   X

   cytoplasm

   Amount

   0

   FALSE

   FALSE

   0

   FALSE

   UNKNOWN

   inside

   Y

   Y

   cytoplasm

   Amount

   1

   FALSE

   FALSE

   0

   FALSE

   UNKNOWN

   inside

   Z

   Z

   cytoplasm

   Amount

   1

   FALSE

   FALSE

   0

   FALSE

2. Set the Kinetic Law at "math" column in "Raction" list.
   

   type	id	name	reversible	fast	reactants	products	modifiers	math
   STATE_TRANSITION	Reaction1	Reaction1	FALSE	FALSE	EmptySet	C		vi
   STATE_TRANSITION	Reaction2	Reaction2	FALSE	FALSE	C	EmptySet		C*kd
   STATE_TRANSITION	Reaction3	Reaction3	FALSE	FALSE	C	EmptySet		C*vd*X/(C+kd)
   STATE_TRANSITION	Reaction4	Reaction4	FALSE	FALSE	EmptySet	Y		VS
   STATE_TRANSITION	Reaction5	Reaction5	FALSE	FALSE	Y	EmptySet		d1*Y
   STATE_TRANSITION	Reaction6	Reaction6	FALSE	FALSE	C,Y	Z		a1*C*Y
   STATE_TRANSITION	Reaction7	Reaction7	FALSE	FALSE	Z	C,Y		a2*Z
   STATE_TRANSITION	Reaction8	Reaction8	FALSE	FALSE	Z	Y		Z*alpha
   STATE_TRANSITION	Reaction9	Reaction9	FALSE	FALSE	Z	C		Z*alpha
   STATE_TRANSITION	Reaction10	Reaction10	FALSE	FALSE	EmptySet	M		(1-M)*VM1*C/(1+K1-M)*(Kc+C)
   STATE_TRANSITION	Reaction11	Reaction11	FALSE	FALSE	EmptySet	X		VM3*(1-X)*M/(1+K3-X)
   STATE_TRANSITION	Reaction12	Reaction12	FALSE	FALSE	M	EmptySet		M*V2/(K2+M)
   STATE_TRANSITION	Reaction13	Reaction13	FALSE	FALSE	X	EmptySet		V4*X/(K4+X)

3. Set the Parameters
   

   scope	id	name	value	units	constant
   local:Reaction(Reaction1)	vi		0.025		TRUE
   local:Reaction(Reaction2)	kd		0.01		TRUE
   local:Reaction(Reaction3)	kd		0.01		TRUE
   local:Reaction(Reaction3)	vd		0.25		TRUE
   local:Reaction(Reaction4)	VS		0		TRUE
   local:Reaction(Reaction5)	d1		0.05		TRUE
   local:Reaction(Reaction6)	a1		0.5		TRUE
   local:Reaction(Reaction7)	a2		0.5		TRUE
   local:Reaction(Reaction8)	alpha		0.1		TRUE
   local:Reaction(Reaction9)	alpha		0.1		TRUE
   local:Reaction(Reaction10)	K1		0.005		TRUE
   local:Reaction(Reaction10)	Kc		0.3		TRUE
   local:Reaction(Reaction10)	VM1		3		TRUE
   local:Reaction(Reaction11)	K3		0.005		TRUE
   local:Reaction(Reaction11)	VM3		1		TRUE
   local:Reaction(Reaction12)	K2		0.005		TRUE
   local:Reaction(Reaction12)	V2		1.5		TRUE
   local:Reaction(Reaction13)	K4		0.005		TRUE
   local:Reaction(Reaction13)	V4		0.5		TRUE

2. Run Simulator

1. Select "Simulation" - "Control Panel " menu of CellDesigner.
   The ControlPanel screen appears.
2. Set [End Time] and [Number of Points].
3. Click [Execute] button at the bottom.
   
   You can also conduct "change initial quantities of the species and parameters ", "change amount at the specific time for simulation", "parameter scan", "interactive simulation" on the Control Panel.
   
4. To save the plot image, select [File]-[Save Image/Print] menu of the ControlPanel.
   The Image Config Dialog window will appear.
5. Click [Config] button to specify the detail appearance of the plot image, such as title, legend and background colors.
6. Click [Save Image]. The image can be saved in BMP, PNG, TIFF, PNM, and JPEG.
7. Click [Print] to print the image as specified.