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example.bngl
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## title: FceRI_ji.bngl
## description: Model of FceRI (the high affinity receptor for IgE) signaling network as described by
# Faeder et al. (2003) [J. Immunol., 170, 3769-3781].
begin model
begin parameters
Na 6.02e23 # Avogadro's number
Vec 1e-9 # Volume of extracellular space
lig_conc 1e-9 # Ligand concentration - molar
Lig_tot lig_conc*Na*Vec # units: molecules
Rec_tot 4.0e2 # units: molecules # Note: these copy numbers have been reduced by a factor of 1000
Lyn_tot 2.8e1 # units: molecules
Syk_tot 4.0e2 # units: molecules
kp1 1.32845238e-7 # units: /molecule/s
km1 0.01 # units: /s
kp2 2.5e-1 # units: /molecule/s
km2 0.01 # units: /s
kpL 5e-2 # units: /molecule/s
kmL 20 # units: /s
kpLs 5e-2 # units: /molecule/s
kmLs 0.12 # units: /s
kpS 6e-2 # units: /molecule/s
kmS 0.13 # units: /s
kpSs 6e-2 # units: /molecule/s
kmSs 0.13 # units: /s
pLb 30 # units: /s
pLbs 100 # units: /s
pLg 1 # units: /s
pLgs 3 # units: /s
pLS 30 # units: /s
pLSs 100 # units: /s
pSS 100 # units: /s
pSSs 200 # units: /s
dm 20 # units: /s
dc 20 # units: /s
end parameters
begin molecule types
Lig(l,l)
Lyn(U,SH2)
Syk(tSH2,l~Y~pY,a~Y~pY)
Rec(a,b~Y~pY,g~Y~pY)
end molecule types
begin species
Lig(l,l) 0 # Lig_tot - set to non-zero value after pre-equil period
Lyn(U,SH2) Lyn_tot
Syk(tSH2,l~Y,a~Y) Syk_tot
Rec(a,b~Y,g~Y) Rec_tot
end species
begin observables
Molecules LynFree Lyn(U,SH2)
Molecules RecMon Rec(a), Rec(a!1).Lig(l!1,l)
Molecules RecDim Rec().Rec()
Molecules RecPbeta Rec(b~pY!?)
Molecules RecPgamma Rec(g~pY), Rec(g~pY!+)
Molecules RecSyk Rec(g~pY!1).Syk(tSH2!1)
Molecules RecSykPS Rec(g~pY!1).Syk(tSH2!1,a~pY)
end observables
begin reaction rules
# Ligand-receptor binding
R1: Rec(a) + Lig(l,l) <-> Rec(a!1).Lig(l!1,l) kp1, km1
# Receptor-aggregation
R2: Rec(a) + Lig(l,l!+) <-> Rec(a!2).Lig(l!2,l!+) kp2, km2
# Constitutive Lyn-receptor binding
R3: Rec(b~Y) + Lyn(U,SH2) <-> Rec(b~Y!1).Lyn(U!1,SH2) kpL, kmL
# Transphosphorylation of beta by constitutive Lyn
R4: Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,b~Y) -> Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,b~pY) pLb
# Transphosphorylation of gamma by constitutive Lyn
R5: Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~Y) -> Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~pY) pLg
# Lyn-receptor binding through SH2 domain
R6: Rec(b~pY) + Lyn(U,SH2) <-> Rec(b~pY!1).Lyn(U,SH2!1) kpLs, kmLs
# Transphosphorylation of beta by SH2-bound Lyn
R7: Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,b~Y) -> Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,b~pY) pLbs
# Transphosphorylation of gamma by SH2-bound Lyn
R8: Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~Y) -> Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~pY) pLgs
# Syk-receptor binding through tSH2 domain
R9: Rec(g~pY) + Syk(tSH2) <-> Rec(g~pY!1).Syk(tSH2!1) kpS, kmS
# Transphosphorylation of Syk by constitutive Lyn
R10: Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~Y) -> Lig(l!1,l!2).Lyn(U!3,SH2).Rec(a!2,b~Y!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~pY) pLS
# Transphosphorylation of Syk by SH2-bound Lyn
R11: Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~Y) -> Lig(l!1,l!2).Lyn(U,SH2!3).Rec(a!2,b~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,l~pY) pLSs
# Transphosphorylation of Syk by Syk not phosphorylated on aloop
R12: Lig(l!1,l!2).Syk(tSH2!3,a~Y).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~Y) -> Lig(l!1,l!2).Syk(tSH2!3,a~Y).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~pY) pSS
# Transphosphorylation of Syk by Syk phosphorylated on aloop
R13: Lig(l!1,l!2).Syk(tSH2!3,a~pY).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~Y) -> Lig(l!1,l!2).Syk(tSH2!3,a~pY).Rec(a!2,g~pY!3).Rec(a!1,g~pY!4).Syk(tSH2!4,a~pY) pSSs
# Dephosphorylation of Rec beta
R14: Rec(b~pY) -> Rec(b~Y) dm
# Dephosphorylation of Rec gamma
R15: Rec(g~pY) -> Rec(g~Y) dm
# Dephosphorylation of Syk at membrane
R16: Syk(tSH2!+,l~pY) -> Syk(tSH2!+,l~Y) dm
R17: Syk(tSH2!+,a~pY) -> Syk(tSH2!+,a~Y) dm
# Dephosphorylation of Syk in cytosol
R18: Syk(tSH2,l~pY) -> Syk(tSH2,l~Y) dc
R19: Syk(tSH2,a~pY) -> Syk(tSH2,a~Y) dc
end reaction rules
end model
## actions ##
generate_network({overwrite=>1})
# Pre-equilibration
simulate({method=>"ode",t_end=>10,n_steps=>10,atol=>1e-8,rtol=>1e-8})
# Addition of ligand
setConcentration("Lig(l,l)", "Lig_tot")
simulate({method=>"ode",t_end=>100,n_steps=>90,atol=>1e-8,rtol=>1e-8,continue=>1})