//Created by libAntimony v2.4 model garmendiatorres_2007__environment(time_) // Variable initializations: time_ = ; end model garmendiatorres_2007__V1(GEFt, V_1) // Assignment Rules: V_1 := V_max1 / GEFt; // Variable initializations: V_max1 = 1; GEFt = 4; end model garmendiatorres_2007__V2(Str, GEFt, V_2) // Assignment Rules: V_2 := (Str * V_max2) / GEFt; // Variable initializations: Str = 1; V_max2 = 1; GEFt = ; end model garmendiatorres_2007__V3(PKAt, GAPt, V_3) // Assignment Rules: V_3 := (k_c3 * PKAt) / GAPt; // Variable initializations: k_c3 = 3.5; PKAt = 0.3; GAPt = 1.5; end model garmendiatorres_2007__V4(GAPt, V_4) // Assignment Rules: V_4 := V_max4 / GAPt; // Variable initializations: V_max4 = 1.3; GAPt = ; end model garmendiatorres_2007__V5(GEFt, RASt, V_5) // Assignment Rules: V_5 := (k_gef * GEFt) / RASt; // Variable initializations: k_gef = 240; GEFt = ; RASt = 250; end model garmendiatorres_2007__V6(GAPt, RASt, V_6) // Assignment Rules: V_6 := (k_gap * GAPt) / RASt; // Variable initializations: k_gap = 600; GAPt = ; RASt = ; end model garmendiatorres_2007__V7(PKAt, PDEt, V_7) // Assignment Rules: V_7 := (k_c7 * PKAt) / PDEt; // Variable initializations: k_c7 = 3.333; PKAt = ; PDEt = 0.5; end model garmendiatorres_2007__V8(PDEt, V_8) // Assignment Rules: V_8 := V_max8 / PDEt; // Variable initializations: V_max8 = 1.5; PDEt = ; end model garmendiatorres_2007__VPKAact(a, r, R2C2, cAMP, C, R2cAMP2, PKAt, V_PKAact) // Assignment Rules: V_PKAact := a * R2C2 * power(cAMP, 2) - r * C * R2cAMP2 * power(PKAt, 2) * 1; // Variable initializations: a = 1; r = 1; R2C2 = ; cAMP = ; C = ; R2cAMP2 = ; PKAt = ; end model garmendiatorres_2007__holoenzyme_R_cAMP(R2C2, R2cAMP2) // Assignment Rules: R2cAMP2 := 1 - R2C2; // Variable initializations: R2C2 = ; end model garmendiatorres_2007__C_subunit(R2C2, C) // Assignment Rules: C := 2 * (1 - R2C2); // Variable initializations: R2C2 = ; end model garmendiatorres_2007__active_GEF(V_1, V_2, GEFa, time_) // Rate Rules: GEFa' = (V_1 * (1 - GEFa)) / (K_1 + (1 - GEFa)) - (V_2 * GEFa) / (K_2 + GEFa); // Variable initializations: V_1 = ; V_2 = ; K_1 = 0.05; K_2 = 0.05; GEFa = 0.36; time_ = ; end model garmendiatorres_2007__active_GAP(V_3, V_4, C, GAPa, time_) // Rate Rules: GAPa' = (V_3 * C * (1 - GAPa)) / (K_3 + (1 - GAPa)) - (V_4 * GAPa) / (K_4 + GAPa); // Variable initializations: V_3 = ; V_4 = ; C = ; K_3 = 0.01; K_4 = 0.01; GAPa = 0.5; time_ = ; end model garmendiatorres_2007__RAS_to_GTP(V_5, V_6, GEFa, GAPa, RGTP, time_) // Rate Rules: RGTP' = (V_5 * GEFa * (1 - RGTP)) / (K_5 + (1 - RGTP)) - (V_6 * GAPa * RGTP) / (K_6 + RGTP); // Variable initializations: K_5 = 0.001; K_6 = 0.001; V_5 = ; V_6 = ; GEFa = ; GAPa = ; RGTP = 0.1; time_ = ; end model garmendiatorres_2007__adenylate_cyclase(RGTP, RASt, CYCLa, time_) // Rate Rules: CYCLa' = k_a * RGTP * RASt * (1 - CYCLa) - k_i * CYCLa; // Variable initializations: k_a = 0.01; k_i = 1; RGTP = ; RASt = ; CYCLa = 0.1; time_ = ; end model garmendiatorres_2007__active_PDE(V_7, V_8, C, PDEa, time_) // Rate Rules: PDEa' = (V_7 * C * (1 - PDEa)) / (K_7 + (1 - PDEa)) - (V_8 * PDEa) / (K_8 + PDEa); // Variable initializations: V_7 = ; V_8 = ; C = ; K_7 = 0.01; K_8 = 0.01; PDEa = 0.5; time_ = ; end model garmendiatorres_2007__cyclic_AMP(CYCLa, PDEt, PDEa, PKAt, V_PKAact, cAMP, time_) // Rate Rules: cAMP' = (k_s * CYCLa * CYCLt - (k_d * PDEt * PDEa * cAMP) / (K_md + cAMP)) - 2 * V_PKAact * PKAt; // Variable initializations: k_s = 4; k_d = 100; CYCLa = ; CYCLt = 0.7; PDEt = ; PDEa = ; PKAt = ; K_md = 20; V_PKAact = ; cAMP = 1; time_ = ; end model garmendiatorres_2007__holoenzyme_R_C(a, r, C, PKAt, cAMP, R2cAMP2, R2C2, time_) // Rate Rules: R2C2' = - a * R2C2 * power(cAMP, 2) + r * power(C, 2) * R2cAMP2 * power(PKAt, 2) * 1; // Variable initializations: a = ; r = ; C = ; PKAt = ; cAMP = ; R2cAMP2 = ; R2C2 = 0.5; time_ = ; end model garmendiatorres_2007__V9(PKAt, MSNt, V_9) // Assignment Rules: V_9 := (k_c9 * PKAt) / MSNt; // Variable initializations: k_c9 = 3.333; PKAt = ; MSNt = 1; end model garmendiatorres_2007__V10(Str, MSNt, V_10) // Assignment Rules: V_10 := (Str * V_max10) / MSNt; // Variable initializations: Str = ; V_max10 = 0.6; MSNt = ; end model garmendiatorres_2007__V11(PKAt, MSNt, V_11) // Assignment Rules: V_11 := (k_c11 * PKAt) / MSNt; // Variable initializations: k_c11 = 3.333; PKAt = ; MSNt = ; end model garmendiatorres_2007__V12(Str, MSNt, V_12) // Assignment Rules: V_12 := (Str * V_max12) / MSNt; // Variable initializations: Str = ; V_max12 = 2; MSNt = ; end model garmendiatorres_2007__cytosol(k_t1, k_t2, K_11, K_12, V_11, V_12, C, MN, MCP, MC, time_) // Rate Rules: MC' = ((- k_t1 * MC + k_t2 * MN) - (V_11 * C * MC) / (K_11 + MC)) + (V_12 * MCP) / (K_12 + MCP); // Variable initializations: k_t1 = 10; k_t2 = 0.001; K_11 = 0.05; K_12 = 0.05; V_11 = ; V_12 = ; C = ; MN = ; MCP = ; MC = 0.25; time_ = ; end model garmendiatorres_2007__nucleus(k_t1, k_t2, K_9, K_10, V_9, V_10, C, MC, MNP, MN, time_) // Rate Rules: MN' = ((k_t1 * MC - k_t2 * MN) - (V_9 * C * MN) / (K_9 + MN)) + (V_10 * MNP) / (K_10 + MNP); // Variable initializations: k_t1 = ; k_t2 = ; K_9 = 0.05; K_10 = 0.05; V_9 = ; V_10 = ; C = ; MC = ; MNP = ; MN = 0.25; time_ = ; end model garmendiatorres_2007__nucleus_phos(k_t3, k_t4, K_9, K_10, V_9, V_10, C, MCP, MN, MNP, time_) // Rate Rules: MNP' = (((V_9 * C * MN) / (K_9 + MN) - (V_10 * MNP) / (K_10 + MNP)) + k_t3 * MCP) - k_t4 * MNP; // Variable initializations: k_t3 = 0.001; k_t4 = 10; K_9 = ; K_10 = ; V_9 = ; V_10 = ; C = ; MCP = ; MN = ; MNP = 0.25; time_ = ; end model garmendiatorres_2007__cytosol_phos(k_t3, k_t4, K_11, K_12, V_11, V_12, C, MNP, MC, MCP, time_) // Rate Rules: MCP' = (- k_t3 * MCP + k_t4 * MNP + (V_11 * C * MC) / (K_11 + MC)) - (V_12 * MCP) / (K_12 + MCP); // Variable initializations: k_t3 = ; k_t4 = ; K_11 = ; K_12 = ; V_11 = ; V_12 = ; C = ; MNP = ; MC = ; MCP = 0.25; time_ = ; end model garmendiatorres_2007__Mcyto(MC, MCP, M_cyto) // Assignment Rules: M_cyto := MC + MCP; // Variable initializations: MC = ; MCP = ; end model garmendiatorres_2007__Mnucl(MN, MNP, M_nucl) // Assignment Rules: M_nucl := MN + MNP; // Variable initializations: MN = ; MNP = ; end model *garmendiatorres_2007____main() // Sub-modules, and any changes to those submodules: environment: garmendiatorres_2007__environment(time_); V1: garmendiatorres_2007__V1(GEFt, V_1); V2: garmendiatorres_2007__V2(Str, GEFt, V_2); V3: garmendiatorres_2007__V3(PKAt, GAPt, V_3); V4: garmendiatorres_2007__V4(GAPt, V_4); V5: garmendiatorres_2007__V5(GEFt, RASt, V_5); V6: garmendiatorres_2007__V6(GAPt, RASt, V_6); V7: garmendiatorres_2007__V7(PKAt, PDEt, V_7); V8: garmendiatorres_2007__V8(PDEt, V_8); VPKAact: garmendiatorres_2007__VPKAact(a, r, R2C2, cAMP, C, R2cAMP2, PKAt, V_PKAact); holoenzyme_R_cAMP: garmendiatorres_2007__holoenzyme_R_cAMP(R2C2, R2cAMP2); C_subunit: garmendiatorres_2007__C_subunit(R2C2, C); active_GEF: garmendiatorres_2007__active_GEF(V_1, V_2, GEFa, time_); active_GAP: garmendiatorres_2007__active_GAP(V_3, V_4, C, GAPa, time_); RAS_to_GTP: garmendiatorres_2007__RAS_to_GTP(V_5, V_6, GEFa, GAPa, RGTP, time_); adenylate_cyclase: garmendiatorres_2007__adenylate_cyclase(RGTP, RASt, CYCLa, time_); active_PDE: garmendiatorres_2007__active_PDE(V_7, V_8, C, PDEa, time_); cyclic_AMP: garmendiatorres_2007__cyclic_AMP(CYCLa, PDEt, PDEa, PKAt, V_PKAact, cAMP, time_); holoenzyme_R_C: garmendiatorres_2007__holoenzyme_R_C(a, r, C, PKAt, cAMP, R2cAMP2, R2C2, time_); V9: garmendiatorres_2007__V9(PKAt, MSNt, V_9); V10: garmendiatorres_2007__V10(Str, MSNt, V_10); V11: garmendiatorres_2007__V11(PKAt, MSNt, V_11); V12: garmendiatorres_2007__V12(Str, MSNt, V_12); cytosol: garmendiatorres_2007__cytosol(k_t1, k_t2, K_11, K_12, V_11, V_12, C, MN, MCP, MC, time_); nucleus: garmendiatorres_2007__nucleus(k_t1, k_t2, K_9, K_10, V_9, V_10, C, MC, MNP, MN, time_); nucleus_phos: garmendiatorres_2007__nucleus_phos(k_t3, k_t4, K_9, K_10, V_9, V_10, C, MCP, MN, MNP, time_); cytosol_phos: garmendiatorres_2007__cytosol_phos(k_t3, k_t4, K_11, K_12, V_11, V_12, C, MNP, MC, MCP, time_); Mcyto: garmendiatorres_2007__Mcyto(MC, MCP, M_cyto); Mnucl: garmendiatorres_2007__Mnucl(MN, MNP, M_nucl); end