(* Generated by JWS Online *) (* This is an experimental feature of JWS Online. Please report any mistakes.*) (* Note that the following notable SBML entities or features are not supported in notebook outputyet: *) (* Events *) (* Constraints *) (* Units and UnitDefinitions *) (* AlgebraicRules *) (* conversionFactors *) variables = { AC\[LetterSpace]PKA\[LetterSpace]cyto\[LetterSpace]mem[t], AC\[LetterSpace]active\[LetterSpace]cyto\[LetterSpace]mem[t], AC\[LetterSpace]cyto\[LetterSpace]mem[t], AMP\[LetterSpace]cyto[t], ATP\[LetterSpace]cyto[t], BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[t], BAR\[LetterSpace]cyto\[LetterSpace]mem[t], B\[LetterSpace]Raf\[LetterSpace]active\[LetterSpace]cyto[t], B\[LetterSpace]Raf\[LetterSpace]cyto[t], GRK\[LetterSpace]bg\[LetterSpace]cyto[t], GRK\[LetterSpace]cyto[t], G\[LetterSpace]GDP\[LetterSpace]cyto[t], G\[LetterSpace]a\[LetterSpace]s\[LetterSpace]cyto[t], G\[LetterSpace]protein\[LetterSpace]cyto[t], MAPK\[LetterSpace]active\[LetterSpace]cyto[t], MAPK\[LetterSpace]cyto[t], MEK\[LetterSpace]active\[LetterSpace]cyto[t], MEK\[LetterSpace]cyto[t], PDE4\[LetterSpace]P\[LetterSpace]cyto[t], PDE4\[LetterSpace]cyto[t], PDE\[LetterSpace]high\[LetterSpace]km\[LetterSpace]cyto[t], PKA\[LetterSpace]cyto[t], PP2A\[LetterSpace]cyto[t], PP\[LetterSpace]PDE\[LetterSpace]cyto[t], PTP\[LetterSpace]PKA\[LetterSpace]cyto[t], PTP\[LetterSpace]PP\[LetterSpace]cyto[t], PTP\[LetterSpace]cyto[t], R2C2\[LetterSpace]cyto[t], bg\[LetterSpace]cyto[t], c2\[LetterSpace]R2C2\[LetterSpace]cyto[t], c3\[LetterSpace]R2C2\[LetterSpace]cyto[t], cAMP\[LetterSpace]cyto[t], c\[LetterSpace]R2C2\[LetterSpace]cyto[t], iso\[LetterSpace]BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[t], iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t], iso\[LetterSpace]BAR\[LetterSpace]p\[LetterSpace]cyto\[LetterSpace]mem[t], iso\[LetterSpace]extra[t] }; initialValues = { AC\[LetterSpace]PKA\[LetterSpace]cyto\[LetterSpace]mem[0] == 0.0, AC\[LetterSpace]active\[LetterSpace]cyto\[LetterSpace]mem[0] == 0.0, AC\[LetterSpace]cyto\[LetterSpace]mem[0] == 300.0, AMP\[LetterSpace]cyto[0] == 3010000.0, ATP\[LetterSpace]cyto[0] == 3010000.0, BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[0] == 0.0, BAR\[LetterSpace]cyto\[LetterSpace]mem[0] == 94.0, B\[LetterSpace]Raf\[LetterSpace]active\[LetterSpace]cyto[0] == 0.0, B\[LetterSpace]Raf\[LetterSpace]cyto[0] == 120.4, GRK\[LetterSpace]bg\[LetterSpace]cyto[0] == 0.0, GRK\[LetterSpace]cyto[0] == 0.602, G\[LetterSpace]GDP\[LetterSpace]cyto[0] == 0.0, G\[LetterSpace]a\[LetterSpace]s\[LetterSpace]cyto[0] == 0.0, G\[LetterSpace]protein\[LetterSpace]cyto[0] == 2167.2, MAPK\[LetterSpace]active\[LetterSpace]cyto[0] == 0.0, MAPK\[LetterSpace]cyto[0] == 216.72, MEK\[LetterSpace]active\[LetterSpace]cyto[0] == 0.0, MEK\[LetterSpace]cyto[0] == 108.36, PDE4\[LetterSpace]P\[LetterSpace]cyto[0] == 0.0, PDE4\[LetterSpace]cyto[0] == 240.8, PDE\[LetterSpace]high\[LetterSpace]km\[LetterSpace]cyto[0] == 301.0, PKA\[LetterSpace]cyto[0] == 0.0, PP2A\[LetterSpace]cyto[0] == 60.2, PP\[LetterSpace]PDE\[LetterSpace]cyto[0] == 120.4, PTP\[LetterSpace]PKA\[LetterSpace]cyto[0] == 0.0, PTP\[LetterSpace]PP\[LetterSpace]cyto[0] == 60.2, PTP\[LetterSpace]cyto[0] == 120.4, R2C2\[LetterSpace]cyto[0] == 120.4, bg\[LetterSpace]cyto[0] == 0.0, c2\[LetterSpace]R2C2\[LetterSpace]cyto[0] == 0.0, c3\[LetterSpace]R2C2\[LetterSpace]cyto[0] == 0.0, cAMP\[LetterSpace]cyto[0] == 0.0, c\[LetterSpace]R2C2\[LetterSpace]cyto[0] == 0.0, iso\[LetterSpace]BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[0] == 0.0, iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[0] == 0.0, iso\[LetterSpace]BAR\[LetterSpace]p\[LetterSpace]cyto\[LetterSpace]mem[0] == 0.0, iso\[LetterSpace]extra[0] == 6020.0 }; rates = { A1, A2, AC\[LetterSpace]activation, AC\[LetterSpace]active, AC\[LetterSpace]basal, B1, B2, GRK, GRK\[LetterSpace]bg, GTPase, G\[LetterSpace]binds\[LetterSpace]BAR, G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR, MEK\[LetterSpace]activates\[LetterSpace]MAPK, PDE4, PKA\[LetterSpace]P\[LetterSpace]PDE, PKA\[LetterSpace]P\[LetterSpace]PTP, PKA\[LetterSpace]activates\[LetterSpace]Raf, PPase\[LetterSpace]MAPK, PPase\[LetterSpace]Raf, PPase\[LetterSpace]mek, PTP, PTP\[LetterSpace]PKA, Raf\[LetterSpace]activates\[LetterSpace]MEK, activate\[LetterSpace]Gs, bg\[LetterSpace]binds\[LetterSpace]GRK, highKM\[LetterSpace]PDE, iso\[LetterSpace]binds\[LetterSpace]BAR, iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g, pde4\[LetterSpace]p, pp2a\[LetterSpace]4, pp\[LetterSpace]ptp, trimer }; rateEquations = { A1 -> (cyto*(-0.00166112956810631*A1\[LetterSpace]Kr*c3\[LetterSpace]R2C2\[LetterSpace]cyto[t] + 2.7593514420370556*^-6*A1\[LetterSpace]Kf*c2\[LetterSpace]R2C2\[LetterSpace]cyto[t]*cAMP\[LetterSpace]cyto[t]))/KMOLE, A2 -> (cyto*(2.7593514420370556*^-6*A2\[LetterSpace]Kf*c3\[LetterSpace]R2C2\[LetterSpace]cyto[t]*cAMP\[LetterSpace]cyto[t] - 0.00166112956810631*A2\[LetterSpace]Kr*PKA\[LetterSpace]cyto[t]))/KMOLE, AC\[LetterSpace]activation -> cyto\[LetterSpace]mem*(-(AC\[LetterSpace]activation\[LetterSpace]Kr\[LetterSpace]AC\[LetterSpace]activation*AC\[LetterSpace]active\[LetterSpace]cyto\[LetterSpace]mem[t]) + 0.00166112956810631*AC\[LetterSpace]activation\[LetterSpace]Kf\[LetterSpace]AC\[LetterSpace]activation*AC\[LetterSpace]cyto\[LetterSpace]mem[t]*G\[LetterSpace]a\[LetterSpace]s\[LetterSpace]cyto[t]), AC\[LetterSpace]active -> (0.00166112956810631*cyto\[LetterSpace]mem*Vmax\[LetterSpace]AC\[LetterSpace]active\[LetterSpace]AC\[LetterSpace]active*ATP\[LetterSpace]cyto[t])/(AC\[LetterSpace]active\[LetterSpace]Km\[LetterSpace]AC\[LetterSpace]active + 0.00166112956810631*ATP\[LetterSpace]cyto[t]), AC\[LetterSpace]basal -> (0.00166112956810631*cyto\[LetterSpace]mem*Vmax\[LetterSpace]AC\[LetterSpace]basal\[LetterSpace]AC\[LetterSpace]basal*ATP\[LetterSpace]cyto[t])/(AC\[LetterSpace]basal\[LetterSpace]Km\[LetterSpace]AC\[LetterSpace]basal + 0.00166112956810631*ATP\[LetterSpace]cyto[t]), B1 -> (cyto*(-0.00166112956810631*B1\[LetterSpace]Kr*c\[LetterSpace]R2C2\[LetterSpace]cyto[t] + 2.7593514420370556*^-6*B1\[LetterSpace]Kf*cAMP\[LetterSpace]cyto[t]*R2C2\[LetterSpace]cyto[t]))/KMOLE, B2 -> (cyto*(-0.00166112956810631*B2\[LetterSpace]Kr*c2\[LetterSpace]R2C2\[LetterSpace]cyto[t] + 2.7593514420370556*^-6*B2\[LetterSpace]Kf*cAMP\[LetterSpace]cyto[t]*c\[LetterSpace]R2C2\[LetterSpace]cyto[t]))/KMOLE, GRK -> (cyto\[LetterSpace]mem*Vmax\[LetterSpace]grk\[LetterSpace]GRK*iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t])/(GRK\[LetterSpace]Km\[LetterSpace]grk + iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t]), GRK\[LetterSpace]bg -> (cyto\[LetterSpace]mem*Vmax\[LetterSpace]GRK\[LetterSpace]bg\[LetterSpace]GRK\[LetterSpace]bg*iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t])/(GRK\[LetterSpace]bg\[LetterSpace]Km\[LetterSpace]GRK\[LetterSpace]bg + iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t]), GTPase -> (cyto*(0.00166112956810631*GTPase\[LetterSpace]Kf\[LetterSpace]GTPase*G\[LetterSpace]a\[LetterSpace]s\[LetterSpace]cyto[t] - 0.00166112956810631*GTPase\[LetterSpace]Kr\[LetterSpace]GTPase*G\[LetterSpace]GDP\[LetterSpace]cyto[t]))/KMOLE, G\[LetterSpace]binds\[LetterSpace]BAR -> cyto\[LetterSpace]mem*(-(G\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kr\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]BAR*BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[t]) + 0.00166112956810631*G\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kf\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]BAR*BAR\[LetterSpace]cyto\[LetterSpace]mem[t]*G\[LetterSpace]protein\[LetterSpace]cyto[t]), G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR -> cyto\[LetterSpace]mem*(0.00166112956810631*G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR\[LetterSpace]Kf\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR*G\[LetterSpace]protein\[LetterSpace]cyto[t]*iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t] - G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR\[LetterSpace]Kr\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR*iso\[LetterSpace]BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[t]), MEK\[LetterSpace]activates\[LetterSpace]MAPK -> (0.00166112956810631*cyto*Vmax\[LetterSpace]MEK\[LetterSpace]activates\[LetterSpace]MAPK*MAPK\[LetterSpace]cyto[t])/(KMOLE*(MEK\[LetterSpace]activates\[LetterSpace]MAPK\[LetterSpace]Km + 0.00166112956810631*MAPK\[LetterSpace]cyto[t])), PDE4 -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PDE4\[LetterSpace]PDE4*cAMP\[LetterSpace]cyto[t])/(KMOLE*(PDE4\[LetterSpace]Km\[LetterSpace]PDE4 + 0.00166112956810631*cAMP\[LetterSpace]cyto[t])), PKA\[LetterSpace]P\[LetterSpace]PDE -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PKA\[LetterSpace]P\[LetterSpace]PDE*PDE4\[LetterSpace]cyto[t])/(KMOLE*(PKA\[LetterSpace]P\[LetterSpace]PDE\[LetterSpace]Km + 0.00166112956810631*PDE4\[LetterSpace]cyto[t])), PKA\[LetterSpace]P\[LetterSpace]PTP -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PKA\[LetterSpace]P\[LetterSpace]PTP*PTP\[LetterSpace]cyto[t])/(KMOLE*(PKA\[LetterSpace]P\[LetterSpace]PTP\[LetterSpace]Km + 0.00166112956810631*PTP\[LetterSpace]cyto[t])), PKA\[LetterSpace]activates\[LetterSpace]Raf -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PKA\[LetterSpace]activates\[LetterSpace]Raf*B\[LetterSpace]Raf\[LetterSpace]cyto[t])/(KMOLE*(PKA\[LetterSpace]activates\[LetterSpace]Raf\[LetterSpace]Km + 0.00166112956810631*B\[LetterSpace]Raf\[LetterSpace]cyto[t])), PPase\[LetterSpace]MAPK -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PPase\[LetterSpace]MAPK*MAPK\[LetterSpace]active\[LetterSpace]cyto[t])/(KMOLE*(PPase\[LetterSpace]MAPK\[LetterSpace]Km + 0.00166112956810631*MAPK\[LetterSpace]active\[LetterSpace]cyto[t])), PPase\[LetterSpace]Raf -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PPase\[LetterSpace]Raf*B\[LetterSpace]Raf\[LetterSpace]active\[LetterSpace]cyto[t])/(KMOLE*(PPase\[LetterSpace]Raf\[LetterSpace]Km + 0.00166112956810631*B\[LetterSpace]Raf\[LetterSpace]active\[LetterSpace]cyto[t])), PPase\[LetterSpace]mek -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PPase\[LetterSpace]mek*MEK\[LetterSpace]active\[LetterSpace]cyto[t])/(KMOLE*(PPase\[LetterSpace]mek\[LetterSpace]Km + 0.00166112956810631*MEK\[LetterSpace]active\[LetterSpace]cyto[t])), PTP -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PTP*MAPK\[LetterSpace]active\[LetterSpace]cyto[t])/(KMOLE*(PTP\[LetterSpace]Km + 0.00166112956810631*MAPK\[LetterSpace]active\[LetterSpace]cyto[t])), PTP\[LetterSpace]PKA -> (0.00166112956810631*cyto*Vmax\[LetterSpace]PTP\[LetterSpace]PKA*MAPK\[LetterSpace]active\[LetterSpace]cyto[t])/(KMOLE*(PTP\[LetterSpace]PKA\[LetterSpace]Km + 0.00166112956810631*MAPK\[LetterSpace]active\[LetterSpace]cyto[t])), Raf\[LetterSpace]activates\[LetterSpace]MEK -> (0.00166112956810631*cyto*Vmax\[LetterSpace]Raf\[LetterSpace]activates\[LetterSpace]MEK*MEK\[LetterSpace]cyto[t])/(KMOLE*(Raf\[LetterSpace]activates\[LetterSpace]MEK\[LetterSpace]Km + 0.00166112956810631*MEK\[LetterSpace]cyto[t])), activate\[LetterSpace]Gs -> cyto\[LetterSpace]mem*(-2.7593514420370556*^-6*activate\[LetterSpace]Gs\[LetterSpace]Kr\[LetterSpace]activate\[LetterSpace]Gs*bg\[LetterSpace]cyto[t]*G\[LetterSpace]a\[LetterSpace]s\[LetterSpace]cyto[t]*iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t] + activate\[LetterSpace]Gs\[LetterSpace]Kf\[LetterSpace]activate\[LetterSpace]Gs*iso\[LetterSpace]BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[t]), bg\[LetterSpace]binds\[LetterSpace]GRK -> (cyto*(-0.00166112956810631*bg\[LetterSpace]binds\[LetterSpace]GRK\[LetterSpace]Kr\[LetterSpace]bg\[LetterSpace]binds\[LetterSpace]GRK*GRK\[LetterSpace]bg\[LetterSpace]cyto[t] + 2.7593514420370556*^-6*bg\[LetterSpace]binds\[LetterSpace]GRK\[LetterSpace]Kf\[LetterSpace]bg\[LetterSpace]binds\[LetterSpace]GRK*bg\[LetterSpace]cyto[t]*GRK\[LetterSpace]cyto[t]))/KMOLE, highKM\[LetterSpace]PDE -> (0.00166112956810631*cyto*Vmax\[LetterSpace]highKM\[LetterSpace]PDE*cAMP\[LetterSpace]cyto[t])/(KMOLE*(highKM\[LetterSpace]PDE\[LetterSpace]Km + 0.00166112956810631*cAMP\[LetterSpace]cyto[t])), iso\[LetterSpace]binds\[LetterSpace]BAR -> cyto\[LetterSpace]mem*(-(iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kr*iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem[t]) + 0.00166112956810631*iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kf*BAR\[LetterSpace]cyto\[LetterSpace]mem[t]*iso\[LetterSpace]extra[t]), iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g -> cyto\[LetterSpace]mem*(-(iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g\[LetterSpace]Kr*iso\[LetterSpace]BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[t]) + 0.00166112956810631*iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g\[LetterSpace]Kf*BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem[t]*iso\[LetterSpace]extra[t]), pde4\[LetterSpace]p -> (0.00166112956810631*cyto*Vmax\[LetterSpace]pde4\[LetterSpace]p\[LetterSpace]pde4\[LetterSpace]p*cAMP\[LetterSpace]cyto[t])/(KMOLE*(pde4\[LetterSpace]p\[LetterSpace]Km\[LetterSpace]pde4\[LetterSpace]p + 0.00166112956810631*cAMP\[LetterSpace]cyto[t])), pp2a\[LetterSpace]4 -> (0.00166112956810631*cyto*Vmax\[LetterSpace]pp2a\[LetterSpace]4\[LetterSpace]pp2a\[LetterSpace]4*PDE4\[LetterSpace]P\[LetterSpace]cyto[t])/(KMOLE*(pp2a\[LetterSpace]4\[LetterSpace]Km\[LetterSpace]pp2a\[LetterSpace]4 + 0.00166112956810631*PDE4\[LetterSpace]P\[LetterSpace]cyto[t])), pp\[LetterSpace]ptp -> (0.00166112956810631*cyto*Vmax\[LetterSpace]pp\[LetterSpace]ptp*PTP\[LetterSpace]PKA\[LetterSpace]cyto[t])/(KMOLE*(pp\[LetterSpace]ptp\[LetterSpace]Km + 0.00166112956810631*PTP\[LetterSpace]PKA\[LetterSpace]cyto[t])), trimer -> (cyto*(2.7593514420370556*^-6*trimer\[LetterSpace]Kf\[LetterSpace]trimer*bg\[LetterSpace]cyto[t]*G\[LetterSpace]GDP\[LetterSpace]cyto[t] - 0.00166112956810631*trimer\[LetterSpace]Kr\[LetterSpace]trimer*G\[LetterSpace]protein\[LetterSpace]cyto[t]))/KMOLE }; parameters = { KMOLE -> 0.00166112956810631, kcat\[LetterSpace]PKA\[LetterSpace]P\[LetterSpace]PTP -> 0.2, kcat\[LetterSpace]PKA\[LetterSpace]activates\[LetterSpace]Raf -> 10.0, kcat\[LetterSpace]PPase\[LetterSpace]MAPK -> 0.636, kcat\[LetterSpace]PPase\[LetterSpace]Raf -> 5.0, kcat\[LetterSpace]PPase\[LetterSpace]mek -> 5.0, kcat\[LetterSpace]PTP -> 1.06, kcat\[LetterSpace]PTP\[LetterSpace]PKA -> 0.1, kcat\[LetterSpace]pp\[LetterSpace]ptp\[LetterSpace]pp\[LetterSpace]ptp -> 5.0, activate\[LetterSpace]Gs\[LetterSpace]I -> 0.0, activate\[LetterSpace]Gs\[LetterSpace]Kf\[LetterSpace]activate\[LetterSpace]Gs -> 0.025, activate\[LetterSpace]Gs\[LetterSpace]Kr\[LetterSpace]activate\[LetterSpace]Gs -> 0.0, pde4\[LetterSpace]p\[LetterSpace]Km\[LetterSpace]pde4\[LetterSpace]p -> 1.3, PPase\[LetterSpace]Raf\[LetterSpace]Km -> 15.7, iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]I -> 0.0, iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kf -> 1.0, iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kr -> 0.2, PDE4\[LetterSpace]Km\[LetterSpace]PDE4 -> 1.3, bg\[LetterSpace]binds\[LetterSpace]GRK\[LetterSpace]Kf\[LetterSpace]bg\[LetterSpace]binds\[LetterSpace]GRK -> 1.0, bg\[LetterSpace]binds\[LetterSpace]GRK\[LetterSpace]Kr\[LetterSpace]bg\[LetterSpace]binds\[LetterSpace]GRK -> 0.25, MEK\[LetterSpace]activates\[LetterSpace]MAPK\[LetterSpace]Km -> 0.046296, PKA\[LetterSpace]activates\[LetterSpace]Raf\[LetterSpace]Km -> 0.5, AC\[LetterSpace]active\[LetterSpace]I -> 0.0, AC\[LetterSpace]active\[LetterSpace]Km\[LetterSpace]AC\[LetterSpace]active -> 32.0, GTPase\[LetterSpace]Kf\[LetterSpace]GTPase -> 0.06667, GTPase\[LetterSpace]Kr\[LetterSpace]GTPase -> 0.0, trimer\[LetterSpace]Kf\[LetterSpace]trimer -> 6.0, trimer\[LetterSpace]Kr\[LetterSpace]trimer -> 0.0, G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR\[LetterSpace]I -> 0.0, G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR\[LetterSpace]Kf\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR -> 10.0, G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR\[LetterSpace]Kr\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR -> 0.1, A2\[LetterSpace]Kf -> 8.35, A2\[LetterSpace]Kr -> 0.0167, highKM\[LetterSpace]PDE\[LetterSpace]Km -> 15.0, PKA\[LetterSpace]P\[LetterSpace]PTP\[LetterSpace]Km -> 0.1, AC\[LetterSpace]activation\[LetterSpace]I -> 0.0, AC\[LetterSpace]activation\[LetterSpace]Kf\[LetterSpace]AC\[LetterSpace]activation -> 500.0, AC\[LetterSpace]activation\[LetterSpace]Kr\[LetterSpace]AC\[LetterSpace]activation -> 1.0, AC\[LetterSpace]basal\[LetterSpace]I -> 0.0, AC\[LetterSpace]basal\[LetterSpace]Km\[LetterSpace]AC\[LetterSpace]basal -> 1030.0, B1\[LetterSpace]Kf -> 0.0059, B1\[LetterSpace]Kr -> 0.00028, GRK\[LetterSpace]I -> 0.0, GRK\[LetterSpace]Km\[LetterSpace]grk -> 15.0, PKA\[LetterSpace]P\[LetterSpace]PDE\[LetterSpace]Km -> 0.5, Raf\[LetterSpace]activates\[LetterSpace]MEK\[LetterSpace]Km -> 0.15909, PTP\[LetterSpace]PKA\[LetterSpace]Km -> 9.0, B2\[LetterSpace]Kf -> 0.0059, B2\[LetterSpace]Kr -> 0.00028, PTP\[LetterSpace]Km -> 0.46, iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g\[LetterSpace]I -> 0.0, iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g\[LetterSpace]Kf -> 1.0, iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g\[LetterSpace]Kr -> 0.062, PPase\[LetterSpace]MAPK\[LetterSpace]Km -> 0.77, pp2a\[LetterSpace]4\[LetterSpace]Km\[LetterSpace]pp2a\[LetterSpace]4 -> 8.0, pp\[LetterSpace]ptp\[LetterSpace]Km -> 6.0, GRK\[LetterSpace]bg\[LetterSpace]I -> 0.0, GRK\[LetterSpace]bg\[LetterSpace]Km\[LetterSpace]GRK\[LetterSpace]bg -> 4.0, G\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]I -> 0.0, G\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kf\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]BAR -> 0.3, G\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]Kr\[LetterSpace]G\[LetterSpace]binds\[LetterSpace]BAR -> 0.1, PPase\[LetterSpace]mek\[LetterSpace]Km -> 15.7, A1\[LetterSpace]Kf -> 8.35, A1\[LetterSpace]Kr -> 0.0167, cyto -> 1.0, cyto\[LetterSpace]mem -> 0.2, extra -> 0.111111111111111 }; assignments = { Vmax\[LetterSpace]pde4\[LetterSpace]p\[LetterSpace]pde4\[LetterSpace]p -> 0.0332225913621262*PDE4\[LetterSpace]P\[LetterSpace]cyto[t], Vmax\[LetterSpace]PPase\[LetterSpace]mek -> 0.00166112956810631*kcat\[LetterSpace]PPase\[LetterSpace]mek*PP2A\[LetterSpace]cyto[t], Vmax\[LetterSpace]GRK\[LetterSpace]bg\[LetterSpace]GRK\[LetterSpace]bg -> 0.0022259136212624555*GRK\[LetterSpace]bg\[LetterSpace]cyto[t], Vmax\[LetterSpace]pp\[LetterSpace]ptp -> 0.00166112956810631*kcat\[LetterSpace]pp\[LetterSpace]ptp\[LetterSpace]pp\[LetterSpace]ptp*PTP\[LetterSpace]PP\[LetterSpace]cyto[t], Vmax\[LetterSpace]pp2a\[LetterSpace]4\[LetterSpace]pp2a\[LetterSpace]4 -> 0.00830564784053155*PP\[LetterSpace]PDE\[LetterSpace]cyto[t], Vmax\[LetterSpace]PPase\[LetterSpace]MAPK -> 0.00166112956810631*kcat\[LetterSpace]PPase\[LetterSpace]MAPK*PP2A\[LetterSpace]cyto[t], Vmax\[LetterSpace]PTP -> 0.00166112956810631*kcat\[LetterSpace]PTP*PTP\[LetterSpace]cyto[t], Vmax\[LetterSpace]PTP\[LetterSpace]PKA -> 0.00166112956810631*kcat\[LetterSpace]PTP\[LetterSpace]PKA*PTP\[LetterSpace]PKA\[LetterSpace]cyto[t], Vmax\[LetterSpace]Raf\[LetterSpace]activates\[LetterSpace]MEK -> 0.00017441860465116255*B\[LetterSpace]Raf\[LetterSpace]active\[LetterSpace]cyto[t], Vmax\[LetterSpace]PKA\[LetterSpace]P\[LetterSpace]PDE -> 0.0166112956810631*PKA\[LetterSpace]cyto[t], Vmax\[LetterSpace]grk\[LetterSpace]GRK -> 0.00017275747508305623*GRK\[LetterSpace]cyto[t], Vmax\[LetterSpace]AC\[LetterSpace]basal\[LetterSpace]AC\[LetterSpace]basal -> 0.2*AC\[LetterSpace]cyto\[LetterSpace]mem[t], Vmax\[LetterSpace]PKA\[LetterSpace]P\[LetterSpace]PTP -> 0.00166112956810631*kcat\[LetterSpace]PKA\[LetterSpace]P\[LetterSpace]PTP*PKA\[LetterSpace]cyto[t], Vmax\[LetterSpace]highKM\[LetterSpace]PDE -> 0.01328903654485048*PDE\[LetterSpace]high\[LetterSpace]km\[LetterSpace]cyto[t], Vmax\[LetterSpace]AC\[LetterSpace]active\[LetterSpace]AC\[LetterSpace]active -> 8.5*AC\[LetterSpace]active\[LetterSpace]cyto\[LetterSpace]mem[t], Vmax\[LetterSpace]PKA\[LetterSpace]activates\[LetterSpace]Raf -> 0.00166112956810631*kcat\[LetterSpace]PKA\[LetterSpace]activates\[LetterSpace]Raf*PKA\[LetterSpace]cyto[t], Vmax\[LetterSpace]MEK\[LetterSpace]activates\[LetterSpace]MAPK -> 0.0002491694352159465*MEK\[LetterSpace]active\[LetterSpace]cyto[t], Vmax\[LetterSpace]PDE4\[LetterSpace]PDE4 -> 0.01328903654485048*PDE4\[LetterSpace]cyto[t], Vmax\[LetterSpace]PPase\[LetterSpace]Raf -> 0.00166112956810631*kcat\[LetterSpace]PPase\[LetterSpace]Raf*PP2A\[LetterSpace]cyto[t] }; events = { }; speciesAnnotations = { AMP\[LetterSpace]cyto[t]->"http://identifiers.org/chebi/CHEBI:16027", AMP\[LetterSpace]cyto[t]->"http://identifiers.org/kegg.compound/C00020", ATP\[LetterSpace]cyto[t]->"http://identifiers.org/chebi/CHEBI:15422", ATP\[LetterSpace]cyto[t]->"http://identifiers.org/kegg.compound/C00002", G\[LetterSpace]protein\[LetterSpace]cyto[t]->"http://identifiers.org/go/GO:0005834", cAMP\[LetterSpace]cyto[t]->"http://identifiers.org/chebi/CHEBI:17489", cAMP\[LetterSpace]cyto[t]->"http://identifiers.org/kegg.compound/C00575" }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "molecules/um2", "extent" -> "molecules/um2"} }; (* Time evolution *) odes = { AC\[LetterSpace]PKA\[LetterSpace]cyto\[LetterSpace]mem'[t] == 0.0 , AC\[LetterSpace]active\[LetterSpace]cyto\[LetterSpace]mem'[t] == 1.0*AC\[LetterSpace]activation , AC\[LetterSpace]cyto\[LetterSpace]mem'[t] == -1.0*AC\[LetterSpace]activation, AMP\[LetterSpace]cyto'[t] == 1.0*pde4\[LetterSpace]p +1.0*PDE4 +1.0*highKM\[LetterSpace]PDE , ATP\[LetterSpace]cyto'[t] == -1.0*AC\[LetterSpace]active -1.0*AC\[LetterSpace]basal, BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem'[t] == 1.0*G\[LetterSpace]binds\[LetterSpace]BAR -1.0*iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g, BAR\[LetterSpace]cyto\[LetterSpace]mem'[t] == -1.0*iso\[LetterSpace]binds\[LetterSpace]BAR -1.0*G\[LetterSpace]binds\[LetterSpace]BAR, B\[LetterSpace]Raf\[LetterSpace]active\[LetterSpace]cyto'[t] == 1.0*PKA\[LetterSpace]activates\[LetterSpace]Raf -1.0*PPase\[LetterSpace]Raf, B\[LetterSpace]Raf\[LetterSpace]cyto'[t] == 1.0*PPase\[LetterSpace]Raf -1.0*PKA\[LetterSpace]activates\[LetterSpace]Raf, GRK\[LetterSpace]bg\[LetterSpace]cyto'[t] == 1.0*bg\[LetterSpace]binds\[LetterSpace]GRK , GRK\[LetterSpace]cyto'[t] == -1.0*bg\[LetterSpace]binds\[LetterSpace]GRK, G\[LetterSpace]GDP\[LetterSpace]cyto'[t] == 1.0*GTPase -1.0*trimer, G\[LetterSpace]a\[LetterSpace]s\[LetterSpace]cyto'[t] == 1.0*activate\[LetterSpace]Gs -1.0*GTPase -1.0*AC\[LetterSpace]activation, G\[LetterSpace]protein\[LetterSpace]cyto'[t] == 1.0*trimer -1.0*G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR -1.0*G\[LetterSpace]binds\[LetterSpace]BAR, MAPK\[LetterSpace]active\[LetterSpace]cyto'[t] == 1.0*MEK\[LetterSpace]activates\[LetterSpace]MAPK -1.0*PTP\[LetterSpace]PKA -1.0*PTP -1.0*PPase\[LetterSpace]MAPK, MAPK\[LetterSpace]cyto'[t] == 1.0*PTP\[LetterSpace]PKA +1.0*PTP +1.0*PPase\[LetterSpace]MAPK -1.0*MEK\[LetterSpace]activates\[LetterSpace]MAPK, MEK\[LetterSpace]active\[LetterSpace]cyto'[t] == 1.0*Raf\[LetterSpace]activates\[LetterSpace]MEK -1.0*PPase\[LetterSpace]mek, MEK\[LetterSpace]cyto'[t] == 1.0*PPase\[LetterSpace]mek -1.0*Raf\[LetterSpace]activates\[LetterSpace]MEK, PDE4\[LetterSpace]P\[LetterSpace]cyto'[t] == 1.0*PKA\[LetterSpace]P\[LetterSpace]PDE -1.0*pp2a\[LetterSpace]4, PDE4\[LetterSpace]cyto'[t] == 1.0*pp2a\[LetterSpace]4 -1.0*PKA\[LetterSpace]P\[LetterSpace]PDE, PDE\[LetterSpace]high\[LetterSpace]km\[LetterSpace]cyto'[t] == 0.0 , PKA\[LetterSpace]cyto'[t] == 1.0*A2 , PP2A\[LetterSpace]cyto'[t] == 0.0 , PP\[LetterSpace]PDE\[LetterSpace]cyto'[t] == 0.0 , PTP\[LetterSpace]PKA\[LetterSpace]cyto'[t] == 1.0*PKA\[LetterSpace]P\[LetterSpace]PTP -1.0*pp\[LetterSpace]ptp, PTP\[LetterSpace]PP\[LetterSpace]cyto'[t] == 0.0 , PTP\[LetterSpace]cyto'[t] == 1.0*pp\[LetterSpace]ptp -1.0*PKA\[LetterSpace]P\[LetterSpace]PTP, R2C2\[LetterSpace]cyto'[t] == -1.0*B1, bg\[LetterSpace]cyto'[t] == 1.0*activate\[LetterSpace]Gs -1.0*bg\[LetterSpace]binds\[LetterSpace]GRK -1.0*trimer, c2\[LetterSpace]R2C2\[LetterSpace]cyto'[t] == 1.0*B2 -1.0*A1, c3\[LetterSpace]R2C2\[LetterSpace]cyto'[t] == 1.0*A1 -1.0*A2, cAMP\[LetterSpace]cyto'[t] == 1.0*AC\[LetterSpace]active +1.0*AC\[LetterSpace]basal -1.0*pde4\[LetterSpace]p -1.0*PDE4 -1.0*A2 -1.0*highKM\[LetterSpace]PDE -1.0*B1 -1.0*B2 -1.0*A1, c\[LetterSpace]R2C2\[LetterSpace]cyto'[t] == 1.0*B1 -1.0*B2, iso\[LetterSpace]BAR\[LetterSpace]G\[LetterSpace]cyto\[LetterSpace]mem'[t] == 1.0*G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR +1.0*iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g -1.0*activate\[LetterSpace]Gs, iso\[LetterSpace]BAR\[LetterSpace]cyto\[LetterSpace]mem'[t] == 1.0*activate\[LetterSpace]Gs +1.0*iso\[LetterSpace]binds\[LetterSpace]BAR -1.0*G\[LetterSpace]binds\[LetterSpace]iso\[LetterSpace]BAR -1.0*GRK -1.0*GRK\[LetterSpace]bg, iso\[LetterSpace]BAR\[LetterSpace]p\[LetterSpace]cyto\[LetterSpace]mem'[t] == 1.0*GRK +1.0*GRK\[LetterSpace]bg , iso\[LetterSpace]extra'[t] == -1.0*iso\[LetterSpace]binds\[LetterSpace]BAR -1.0*iso\[LetterSpace]binds\[LetterSpace]BAR\[LetterSpace]g }; timeCourse = NDSolve[Join[odes, initialValues]//.rateEquations//.assignments//.parameters, variables, {t, 0, 100}]; (* Steady-state solution initialized with result of time evolution *) findRootEquations = odes /.D[_[t],t]->0; findRootVariables = Partition[Flatten[{#, #/.timeCourse/.t->100} &/@variables],2]; steadyStateVariables = FindRoot[findRootEquations//.rateEquations//.assignments//.parameters, findRootVariables, MaxIterations->100] fluxes = #//.assignments//.parameters/.steadyStateVariables&/@rateEquations (* Plot the time evolution of the variables *) plotTable=Table[Plot[variables[[i]]/.parameters/.timeCourse,{t,0,100},PlotLegends->variables[[i]],PlotRange->Full],{i,Length[variables]}]