Minimal Mitotic Oscillator with Inhibitor

Citation
Gardner TS, Dolnik M, Collins JJ (1998) A theory for controlling cell cycle dynamics using a reversibly binding inhibitor. PNAS 95: 14190-14195. http://www.pnas.org/cgi/content/abstract/95/24/14190
Description
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.
Rate constant       Reaction
a1 = 0.5 C + Y -> Z
a2 = 0.5 Z -> C + Y
d1 = 0.05 Y -> EmptySet
K1 = 0.005 (hill khalf) Comp[M] -> M
K2 = 0.005 (hill khalf) M -> EmptySet
K3 = 0.005 (hill khalf) Comp[X] -> X
K4 = 0.005 (hill khalf) X -> EmptySet
Kc = 0.3 (hill vmax) Comp[M] -> M
kd = 0.01 C -> EmptySet
kd = 0.01 (hill khalf) C + X -> X + EmptySet
V2 = 1.5 (hill vmax) M -> EmptySet
V4 = 0.5 (hill vmax) X -> EmptySet
vd = 0.25 (hill vmax) C + X -> X + EmptySet
vi = 0.025 EmptySet -> C
VM1 = 3 (hill vmax) Comp[M] -> M
VM3 = 1 (hill vmax) Comp[X] -> X
VS = 0 EmptySet -> Y
alpha = 0.1 Z -> C
alpha = 0.1 Z -> Y
Variable IC   ODE
C 0 C'[t] == vi - kd*C[t] - (vd*C[t]*X[t])/( kd + C[t]) - a1*C[t]*Y[t] + a2*Z[t] + alpha* Z[t]
M 0 M'[t] == (VM1*C[t]*(1 - M[t]))/((Kc + C[t])*( 1 + K1 - M[t])) - (V2*M[t])/(K2 + M[t])
X 0 X'[t] == (VM3*M[t]*(1 - X[t]))/(1 + K3 -  X[t]) - (V4*X[t])/(K4 + X[t])
Y 1 Y'[t] == VS - d1*Y[t] - a1*C[t]*Y[t] +  a2*Z[t] + alpha*Z[t]
Z 1 Z'[t] == a1*C[t]*Y[t] - a2*Z[t] - 2*alpha*Z[t]

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