From BioNetWiki
# Base model of Shp2 regulation from Barua, Faeder, and Haugh (2006).
# Copyright 2006, North Carolina State University and Los Alamos National
# Laboratory
# Concentration units are in micromolar; time units are in seconds.
version("2.0.34");
begin parameters
kdim 1000
kopen 10
kclose 500
kon_CSH2 1
koff_CSH2 1
kon_NSH2 1
koff_NSH2 1
kkin_Y1 0.1
kon_PTP 1
koff_PTP 10
kcat_PTP 1
chi_r1 1000
chi_r2 100
chi_r3 1000
chi_r4 1000
chi_r5 100
chi_r6 100
chi_r7 100
chi_r8 1000 # Equals chi_r1*chi_r6/chi_r2
chi_r9 100 # Equals chi_r1*chi_r7/chi_r3
chi_r10 100 # Equals chi_r1*chi_r6/chi_r4
chi_r11 1000 # Equals chi_r1*chi_r7/chi_r5
R_dim 0.025 # R_tot= 2*R_dim
S_tot 0.05
end parameters
begin molecule types
R(DD,Y1~U~P,Y2~P)
S(NSH2~C~O,CSH2,PTP~C~O)
end molecule types
begin species
S(NSH2~C,CSH2,PTP~C) S_tot
# Pre-dimerized receptors
R(DD!1,Y1~U,Y2~P).R(DD!1,Y1~U,Y2~P) R_dim
end species
begin reaction rules
# Intra-complex phosphorylation
R(DD!+,Y1~U) -> R(DD!+,Y1~P) kkin_Y1
# Equilibrium between the closed form and open form of S
S(NSH2~C,PTP~C) <-> S(NSH2~O,PTP~O) kopen,kclose
# Binding of S(CSH2) from cytosol
R(Y2~P) + S(CSH2) <-> R(Y2~P!1).S(CSH2!1) kon_CSH2,koff_CSH2 \
exclude_reactants(2,R)
# Binding of S(NSH2~O) from cytosol
R(Y2~P) + S(NSH2~O) <-> R(Y2~P!1).S(NSH2~O!1) kon_NSH2,koff_NSH2 \
exclude_reactants(2,R)
# Binding of S(PTP~O) from cytosol
R(Y1~P) + S(PTP~O) <-> R(Y1~P!1).S(PTP~O!1) kon_PTP,koff_PTP \
exclude_reactants(2,R)
# Dephosphorylation of R(Y1~P)
R(Y1~P!1).S(PTP~O!1) -> R(Y1~U) + S(PTP~O) kcat_PTP
R(Y1~P!1).S(PTP~O!1) -> R(Y1~U).S(PTP~O) kcat_PTP
# 1 Intra-complex binding: CSH2 bound, association of NSH2 (open) with other receptor
R(Y2~P).S(NSH2~O,CSH2!+,PTP~O) <-> \
R(Y2~P!1).S(NSH2~O!1,CSH2!+,PTP~O) chi_r1*kon_NSH2,koff_NSH2
# 2 Intra-complex binding: CSH2 bound, association of PTP (open) with same receptor
R(Y1~P,Y2~P!1).S(NSH2~O,CSH2!1,PTP~O) <-> \
R(Y1~P!2,Y2~P!1).S(NSH2~O,CSH2!1,PTP~O!2) chi_r2*kon_PTP,koff_PTP
# 3 Intra-complex binding: CSH2 bound, association of PTP (open) with other receptor
R(Y1~P).R(Y2~P!1).S(NSH2~O,CSH2!1,PTP~O) <-> \
R(Y1~P!2).R(Y2~P!1).S(NSH2~O,CSH2!1,PTP~O!2) chi_r3*kon_PTP,koff_PTP
# 4 Intra-complex binding: NSH2 bound, association of CSH2 with other receptor
R(Y2~P).S(NSH2~O!+,CSH2,PTP~O) <-> \
R(Y2~P!1).S(NSH2~O!+,CSH2!1,PTP~O) chi_r1*kon_CSH2,koff_CSH2
# 5 Intra-complex binding: NSH2 bound, association of PTP with other receptor
R(Y1~P).R(Y2~P!1).S(NSH2~O!1,CSH2,PTP~O) <-> \
R(Y1~P!2).R(Y2~P!1).S(NSH2~O!1,CSH2,PTP~O!2) chi_r4*kon_PTP,koff_PTP
# 6 Intracomplex binding: NSH2 bound, association of PTP with same receptor
R(Y1~P,Y2~P!1).S(NSH2~O!1,CSH2,PTP~O) <-> \
R(Y1~P!2,Y2~P!1).S(NSH2~O!1,CSH2,PTP~O!2) chi_r5*kon_PTP,koff_PTP
# 7 Intra-complex binding: PTP bound, association of CSH2 with same receptor
R(Y1~P!1,Y2~P).S(NSH2~O,CSH2,PTP~O!1) <-> \
R(Y1~P!1,Y2~P!2).S(NSH2~O,CSH2!2,PTP~O!1) chi_r2*kon_CSH2,koff_CSH2
# 8 Intra-complex binding: PTP bound, association of CSH2 with other receptor
R(Y1~P!1).R(Y2~P).S(NSH2~O,CSH2,PTP~O!1) <-> \
R(Y1~P!1).R(Y2~P!2).S(NSH2~O,CSH2!2,PTP~O!1) chi_r3*kon_CSH2,koff_CSH2
# 9 Intra-complex binding: PTP bound, association of NSH2 with other receptor
R(Y1~P!1).R(Y2~P).S(NSH2~O,CSH2,PTP~O!1) <-> \
R(Y1~P!1).R(Y2~P!2).S(NSH2~O!2,CSH2,PTP~O!1) chi_r4*kon_NSH2,koff_NSH2
# 10 Intra-complex binding: PTP bound, association of NSH2 with same receptor
R(Y1~P!1,Y2~P).S(NSH2~O,CSH2,PTP~O!1) <-> \
R(Y1~P!1,Y2~P!2).S(NSH2~O!2,CSH2,PTP~O!1) chi_r5*kon_NSH2,koff_NSH2
# 11 Intra-complex binding: CSH2 & NSH2 bound, assoc. of PTP with same receptor as CSH2
R(Y1~P,Y2~P!1).R(Y2~P!2).S(NSH2~O!2,CSH2!1,PTP~O) <-> \
R(Y1~P!3,Y2~P!1).R(Y2~P!2).S(NSH2~O!2,CSH2!1,PTP~O!3) \
chi_r6*kon_PTP,koff_PTP
# 12 Intra-complex binding: CSH2 & NSH2 bound, assoc. of PTP with same receptor as NSH2
R(Y1~P,Y2~P!1).R(Y2~P!2).S(NSH2~O!1,CSH2!2,PTP~O) <-> \
R(Y1~P!3,Y2~P!1).R(Y2~P!2).S(NSH2~O!1,CSH2!2,PTP~O!3) \
chi_r7*kon_PTP,koff_PTP
# 13 Intra-complex binding: CSH2 & PTP bound to the same receptor, assoc. of NSH2
R(Y1~P!1,Y2~P!2).R(Y2~P).S(NSH2~O,CSH2!2,PTP~O!1) <-> \
R(Y1~P!1,Y2~P!2).R(Y2~P!3).S(NSH2~O!3,CSH2!2,PTP~O!1) \
chi_r8*kon_NSH2,koff_NSH2
# 14 Intra-complex binding: CSH2 & PTP bound to different receptors, assoc. of NSH2
R(Y2~P!1).R(Y1~P!2,Y2~P).S(NSH2~O,CSH2!1,PTP~O!2) <-> \
R(Y2~P!1).R(Y1~P!2,Y2~P!3).S(NSH2~O!3,CSH2!1,PTP~O!2) \
chi_r9*kon_NSH2,koff_NSH2
# 15 Intra-complex binding: PTP & NSH2 bound to different receptors, assoc. of CSH2
R(Y2~P!1).R(Y1~P!2,Y2~P).S(NSH2~O!1,CSH2,PTP~O!2) <-> \
R(Y2~P!1).R(Y1~P!2,Y2~P!3).S(NSH2~O!1,CSH2!3,PTP~O!2) \
chi_r10*kon_CSH2,koff_CSH2
# 16 Intra-complex binding: PTP & NSH2 bound to same receptor, assoc. of CSH2
R(Y1~P!1,Y2~P!2).R(Y2~P).S(NSH2~O!2,CSH2,PTP~O!1) <-> \
R(Y1~P!1,Y2~P!2).R(Y2~P!3).S(NSH2~O!2,CSH2!3,PTP~O!1) \
chi_r11*kon_CSH2,koff_CSH2
end reaction rules
begin observables
Molecules pYR R(Y1~P!?)
end observables
generate_network({overwrite=>1});
simulate_ode({t_end=>1000,n_steps=>100,steady_state=>1,atol=>1e-10,rtol=>1e-8,sparse=>0});
