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BIOMD0000000588 - Benson2013 - ranking_drug_targets_NGF_pathway

 

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Reference Publication
Publication ID: 24427523
Benson N, Matsuura T, Smirnov S, Demin O, Jones HM, Dua P, van der Graaf PH.
Systems pharmacology of the nerve growth factor pathway: use of a systems biology model for the identification of key drug targets using sensitivity analysis and the integration of physiology and pharmacology.
Interface Focus 2013 Apr; 3(2): 20120071
Xenologiq Ltd, Unit 7 , Denne Hill Business Park, Canterbury CT4 6HD , UK ; Department of Pharmacokinetics, Dynamics and Metabolism , Pfizer Worldwide R&D , Boston, MA , USA.  [more]
Model
Original Model: BIOMD0000000588.origin
Submitter: Vijayalakshmi Chelliah
Submission ID: MODEL1601290000
Submission Date: 29 Jan 2016 14:20:29 UTC
Last Modification Date: 01 Feb 2017 14:51:04 UTC
Creation Date: 29 Jan 2016 14:30:37 UTC
Encoders:  Vijayalakshmi Chelliah
   Niel Benson
set #1
bqmodel:isDerivedFrom BioModels Database Sasagawa2005_MAPK
PubMed 16418172
bqbiol:hasTaxon Taxonomy Rattus
bqbiol:occursIn Brenda Tissue Ontology PC-12 cell
set #2
bqbiol:isVersionOf Gene Ontology negative regulation of neurotrophin TRK receptor signaling pathway
Gene Ontology nerve growth factor signaling pathway
bqbiol:hasProperty Experimental Factor Ontology pain
Notes
Benson2013 - Identification of key drug targets in nerve growth factor pathway

This model is described in the article:

Benson N, Matsuura T, Smirnov S, Demin O, Jones HM, Dua P, van der Graaf PH.
Interface Focus 2013 Apr; 3(2): 20120071

Abstract:

The nerve growth factor (NGF) pathway is of great interest as a potential source of drug targets, for example in the management of certain types of pain. However, selecting targets from this pathway either by intuition or by non-contextual measures is likely to be challenging. An alternative approach is to construct a mathematical model of the system and via sensitivity analysis rank order the targets in the known pathway, with respect to an endpoint such as the diphosphorylated extracellular signal-regulated kinase concentration in the nucleus. Using the published literature, a model was created and, via sensitivity analysis, it was concluded that, after NGF itself, tropomyosin receptor kinase A (TrkA) was one of the most sensitive druggable targets. This initial model was subsequently used to develop a further model incorporating physiological and pharmacological parameters. This allowed the exploration of the characteristics required for a successful hypothetical TrkA inhibitor. Using these systems models, we were able to identify candidates for the optimal drug targets in the known pathway. These conclusions were consistent with clinical and human genetic data. We also found that incorporating appropriate physiological context was essential to drawing accurate conclusions about important parameters such as the drug dose required to give pathway inhibition. Furthermore, the importance of the concentration of key reactants such as TrkA kinase means that appropriate contextual data are required before clear conclusions can be drawn. Such models could be of great utility in selecting optimal targets and in the clinical evaluation of novel drugs.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 24427523 Submission Date: 29 Jan 2016 14:20:29 UTC Last Modification Date: 01 Feb 2017 14:51:04 UTC Creation Date: 29 Jan 2016 14:30:37 UTC
Mathematical expressions
Reactions
R1 R3 R4 R5
R6 R7 R8 R9
R10 R11 R12 R13
R14 R15 R16 R17
R18 R19 R20 R21
R22 R23 R24 R25
R26 R27 R28 R29
R30 R31 R32 R33
R34 R35 R36 R37
R38 R39 R40 R41
R42 R43 R44 R45
R46 R47 R48 R49
R50 R51 R52 R53
R54 R55 R56 R57
R58 R59 R60 R61
R62 R63 R64 R65
R66 R67 R68 R69
R70 R71 R72 R73
R74 R75 R76 R77
R78 R79 R80 R81
R82 R83 R84 R85
R86 R87 R88 R89
R90 R91 R92 R93
R94 R95 R96 R97
R98 R99 R100 R101
R102 R103 R104 R105
R106 R107 R108 R109
R110 R111 R112 R113
R114 R115 R116 R117
R118 R119 R120 R121
R122 R123 R124 R125
R126 R127 R128 R129
R130 R131 R132 R133
R134 R135 R136 R137
R138 R139 R140 R141
R142 R143 R144 R145
reaction_1 reaction_2 reaction_3 reaction_4
reaction_5 reaction_6 reaction_7 reaction_8
Intercomp mass transfer reaction_9 reaction_10 reaction_14
reaction_15      
Physical entities
Compartments Species
Neuron NGFR L_NGFR pTrkA
pTrkA_endo Shc_pTrkA Shc_pTrkA_endo
pShc_pTrkA pShc_pTrkA_endo Grb2_SOS_pShc_pTrkA
Grb2_SOS_pShc_pTrkA_endo FRS2_pTrkA FRS2_pTrkA_endo
pFRS2_pTrkA pFRS2_pTrkA_endo Crk_C3G_pFRS2_pTrkA
Crk_C3G_pFRS2_pTrkA_endo Shc Grb2_SOS_pShc
FRS2 Crk_C3G Dok
pDok Grb2 SOS
Grb2_SOS Ras_GTP Ras_GDP
B_Raf_Ras_GTP B_Raf c_Raf
Rap1_GTP ppMEKcyt_ERKcyt ppMEKcyt
ppERKcyt dppERKcyt MEKcyt
ERKcyt MEKcyt_ERKcyt pMEKcyt
pMEKcyt_ERKcyt ppMEKnuc_ERKnuc ppMEKnuc
ppERKnuc dppERKnuc MEKnuc
ERKnuc MEKnuc_ERKnuc pMEKnuc
pMEKnuc_ERKnuc c_Raf_Ras_GTP B_Raf_Rap1_GTP
Rap1_GDP Crk C3G
pDok_RasGAP RasGAP Grb2_pSOS
pShc pSOS pFRS2
trkaI_int pro_TrkA L_NGFR_I
NGFR_I NGFR_I_deg L_NGFR_I_deg
     
Interstitial fluid NGFR_interstitial_fluid source NGF
NGFdeg NGFR_L_interstitial_fluid tanezumab
NGF_tanezumab tz_deg trkaI
trkaI_deg    
Global parameters
Km_104 Km_105 Km_106 Km_107
Km_108 Km_109 Km_39 Km_40
Km_41 Km_42 Km_43 Km_44
Km_45 Km_58 Km_59 Km_60
Km_61 Km_62 Km_63 Km_64
Km_70 Km_71 Km_72 Km_81
Km_82 Km_83 Km_84 Km_85
Km_86 Km_87 Km_88 Km_89
Km_90 Km_91 Km_92 Km_93
Km_94 Km_95 Km_96 Km_97
Km_98 MKP3cyt MKP3nuc PP2Acyt
PP2Anuc Rap1GAP Vmax_104 Vmax_105
Vmax_106 Vmax_107 Vmax_108 Vmax_109
Vmax_39 Vmax_40 Vmax_41 Vmax_42
Vmax_43 Vmax_44 Vmax_45 Vmax_58
Vmax_59 Vmax_60 Vmax_61 Vmax_62
Vmax_63 Vmax_64 Vmax_70 Vmax_71
Vmax_72 Vmax_81 Vmax_82 Vmax_83
Vmax_84 Vmax_85 Vmax_86 Vmax_87
Vmax_88 Vmax_89 Vmax_90 Vmax_91
Vmax_92 Vmax_93 Vmax_94 Vmax_95
Vmax_96 Vmax_97 Vmax_98 kb_1
kb_100 kb_101 kb_102 kb_103
kb_18 kb_19 kb_20 kb_21
kb_22 kb_23 kb_24 kb_25
kb_26 kb_27 kb_46 kb_47
kb_48 kb_49 kb_50 kb_55
kb_56 kb_65 kb_66 kb_67
kb_73 kb_74 kb_75 kb_77
kb_78 kb_79 kb_80 kf_1
kf_10 kf_100 kf_101 kf_102
kf_103 kf_11 kf_110 kf_111
kf_112 kf_113 kf_114 kf_115
kf_116 kf_117 kf_118 kf_119
kf_12 kf_120 kf_121 kf_122
kf_123 kf_124 kf_125 kf_126
kf_127 kf_128 kf_129 kf_13
kf_130 kf_131 kf_132 kf_133
kf_134 kf_135 kf_136 kf_137
kf_138 kf_139 kf_14 kf_140
kf_141 kf_142 kf_143 kf_144
kf_145 kf_15 kf_16 kf_17
kf_19 kf_20 kf_21 kf_22
kf_23 kf_24 kf_25 kf_26
kf_27 kf_28 kf_29 kf_3
kf_30 kf_31 kf_32 kf_33
kf_34 kf_35 kf_36 kf_37
kf_38 kf_4 kf_46 kf_47
kf_48 kf_49 kf_5 kf_50
kf_51 kf_52 kf_53 kf_54
kf_55 kf_56 kf_57 kf_6
kf_65 kf_66 kf_67 kf_68
kf_69 kf_7 kf_73 kf_74
kf_75 kf_76 kf_77 kf_78
kf_79 kf_8 kf_80 kf_9
kf_99 kf_18    
Reactions (157)
 
 R1 [pro_TrkA] ↔ [NGFR] + [pro_TrkA];   {pro_TrkA} , {NGFR}
 
 R3 [L_NGFR] → [pTrkA];   {L_NGFR}
 
 R4 [pTrkA] → [pTrkA_endo];   {pTrkA}
 
 R5 [Shc_pTrkA] → [Shc_pTrkA_endo];   {Shc_pTrkA}
 
 R6 [pShc_pTrkA] → [pShc_pTrkA_endo];   {pShc_pTrkA}
 
 R7 [Grb2_SOS_pShc_pTrkA] → [Grb2_SOS_pShc_pTrkA_endo];   {Grb2_SOS_pShc_pTrkA}
 
 R8 [FRS2_pTrkA] → [FRS2_pTrkA_endo];   {FRS2_pTrkA}
 
 R9 [pFRS2_pTrkA] → [pFRS2_pTrkA_endo];   {pFRS2_pTrkA}
 
 R10 [Crk_C3G_pFRS2_pTrkA] → [Crk_C3G_pFRS2_pTrkA_endo];   {Crk_C3G_pFRS2_pTrkA}
 
 R11 [pTrkA_endo] → ;   {pTrkA_endo}
 
 R12 [Shc_pTrkA_endo] → [Shc];   {Shc_pTrkA_endo}
 
 R13 [pShc_pTrkA_endo] → [pShc];   {pShc_pTrkA_endo}
 
 R14 [Grb2_SOS_pShc_pTrkA_endo] → [Grb2_SOS_pShc];   {Grb2_SOS_pShc_pTrkA_endo}
 
 R15 [FRS2_pTrkA_endo] → [FRS2];   {FRS2_pTrkA_endo}
 
 R16 [pFRS2_pTrkA_endo] → [pFRS2];   {pFRS2_pTrkA_endo}
 
 R17 [Crk_C3G_pFRS2_pTrkA_endo] → [Crk_C3G] + [pFRS2];   {Crk_C3G_pFRS2_pTrkA_endo}
 
 R18 [pTrkA] + [Shc] → [Shc_pTrkA];   {Shc} , {pTrkA} , {Shc_pTrkA}
 
 R19 [pTrkA] + [pShc] → [pShc_pTrkA];   {pShc} , {pTrkA} , {pShc_pTrkA}
 
 R20 [pTrkA] + [Grb2_SOS_pShc] → [Grb2_SOS_pShc_pTrkA];   {Grb2_SOS_pShc} , {pTrkA} , {Grb2_SOS_pShc_pTrkA}
 
 R21 [pTrkA_endo] + [Shc] → [Shc_pTrkA_endo];   {Shc} , {pTrkA_endo} , {Shc_pTrkA_endo}
 
 R22 [pTrkA_endo] + [pShc] → [pShc_pTrkA_endo];   {pShc} , {pTrkA_endo} , {pShc_pTrkA_endo}
 
 R23 [pTrkA_endo] + [Grb2_SOS_pShc] → [Grb2_SOS_pShc_pTrkA_endo];   {Grb2_SOS_pShc} , {pTrkA_endo} , {Grb2_SOS_pShc_pTrkA_endo}
 
 R24 [pTrkA] + [FRS2] → [FRS2_pTrkA];   {FRS2} , {pTrkA} , {FRS2_pTrkA}
 
 R25 [pTrkA] + [pFRS2] → [pFRS2_pTrkA];   {pFRS2} , {pTrkA} , {pFRS2_pTrkA}
 
 R26 [pTrkA_endo] + [FRS2] → [FRS2_pTrkA_endo];   {FRS2} , {pTrkA_endo} , {FRS2_pTrkA_endo}
 
 R27 [pTrkA_endo] + [pFRS2] → [pFRS2_pTrkA_endo];   {pFRS2} , {pTrkA_endo} , {pFRS2_pTrkA_endo}
 
 R28 [Shc_pTrkA] → [pShc_pTrkA];   {Shc_pTrkA}
 
 R29 [Shc_pTrkA_endo] → [pShc_pTrkA_endo];   {Shc_pTrkA_endo}
 
 R30 [FRS2_pTrkA] → [pFRS2_pTrkA];   {FRS2_pTrkA}
 
 R31 [FRS2_pTrkA_endo] → [pFRS2_pTrkA_endo];   {FRS2_pTrkA_endo}
 
 R32 [pTrkA] → ;   {pTrkA}
 
 R33 [Shc_pTrkA] → [Shc];   {Shc_pTrkA}
 
 R34 [pShc_pTrkA] → [pShc];   {pShc_pTrkA}
 
 R35 [Grb2_SOS_pShc_pTrkA] → [Grb2_SOS_pShc];   {Grb2_SOS_pShc_pTrkA}
 
 R36 [FRS2_pTrkA] → [FRS2];   {FRS2_pTrkA}
 
 R37 [pFRS2_pTrkA] → [pFRS2];   {pFRS2_pTrkA}
 
 R38 [Crk_C3G_pFRS2_pTrkA] → [Crk_C3G] + [pFRS2];   {Crk_C3G_pFRS2_pTrkA}
 
 R39 [Dok] + [pTrkA] → [pDok] + [pTrkA];   {pTrkA} , {Dok}
 
 R40 [Dok] + [Shc_pTrkA] → [pDok] + [Shc_pTrkA];   {Shc_pTrkA} , {Dok}
 
 R41 [Dok] + [pShc_pTrkA] → [pDok] + [pShc_pTrkA];   {pShc_pTrkA} , {Dok}
 
 R42 [Dok] + [Grb2_SOS_pShc_pTrkA] → [pDok] + [Grb2_SOS_pShc_pTrkA];   {Grb2_SOS_pShc_pTrkA} , {Dok}
 
 R43 [Dok] + [FRS2_pTrkA] → [pDok] + [FRS2_pTrkA];   {FRS2_pTrkA} , {Dok}
 
 R44 [Dok] + [pFRS2_pTrkA] → [pDok] + [pFRS2_pTrkA];   {pFRS2_pTrkA} , {Dok}
 
 R45 [Dok] + [Crk_C3G_pFRS2_pTrkA] → [pDok] + [Crk_C3G_pFRS2_pTrkA];   {Crk_C3G_pFRS2_pTrkA} , {Dok}
 
 R46 [Grb2] + [SOS] → [Grb2_SOS];   {Grb2} , {SOS} , {Grb2_SOS}
 
 R47 [Grb2] + [pSOS] → [Grb2_pSOS];   {Grb2} , {pSOS} , {Grb2_pSOS}
 
 R48 [Grb2_SOS] + [pShc] → [Grb2_SOS_pShc];   {Grb2_SOS} , {pShc} , {Grb2_SOS_pShc}
 
 R49 [pShc_pTrkA] + [Grb2_SOS] → [Grb2_SOS_pShc_pTrkA];   {Grb2_SOS} , {pShc_pTrkA} , {Grb2_SOS_pShc_pTrkA}
 
 R50 [pShc_pTrkA_endo] + [Grb2_SOS] → [Grb2_SOS_pShc_pTrkA_endo];   {Grb2_SOS} , {pShc_pTrkA_endo} , {Grb2_SOS_pShc_pTrkA_endo}
 
 R51 [pShc] → [Shc];   {pShc}
 
 R52 [Grb2_SOS_pShc] → [Shc] + [Grb2_SOS];   {Grb2_SOS_pShc}
 
 R53 [pSOS] → [SOS];   {pSOS}
 
 R54 [Grb2_pSOS] → [Grb2_SOS];   {Grb2_pSOS}
 
 R55 [pDok] + [RasGAP] → [pDok_RasGAP];   {pDok} , {RasGAP} , {pDok_RasGAP}
 
 R56 [pDok] → [Dok];   {pDok} , {Dok}
 
 R57 [Ras_GTP] → [Ras_GDP];   {Ras_GTP}
 
 R58 [Ras_GDP] + [Grb2_SOS_pShc_pTrkA] → [Ras_GTP] + [Grb2_SOS_pShc_pTrkA];   {Grb2_SOS_pShc_pTrkA} , {Ras_GDP}
 
 R59 [SOS] + [dppERKcyt] → [pSOS] + [dppERKcyt];   {dppERKcyt} , {SOS}
 
 R60 [Grb2_SOS_pShc] + [dppERKcyt] → [Grb2_pSOS] + [pShc] + [dppERKcyt];   {dppERKcyt} , {Grb2_SOS_pShc}
 
 R61 [Grb2_SOS] + [dppERKcyt] → [Grb2_pSOS] + [dppERKcyt];   {dppERKcyt} , {Grb2_SOS}
 
 R62 [Ras_GTP] + [pDok_RasGAP] → [Ras_GDP] + [pDok_RasGAP];   {pDok_RasGAP} , {Ras_GTP}
 
 R63 [B_Raf_Ras_GTP] + [pDok_RasGAP] → [Ras_GDP] + [B_Raf] + [pDok_RasGAP];   {pDok_RasGAP} , {B_Raf_Ras_GTP}
 
 R64 [c_Raf_Ras_GTP] + [pDok_RasGAP] → [Ras_GDP] + [c_Raf] + [pDok_RasGAP];   {pDok_RasGAP} , {c_Raf_Ras_GTP}
 
 R65 [Crk] + [C3G] → [Crk_C3G];   {C3G} , {Crk} , {Crk_C3G}
 
 R66 [pFRS2_pTrkA] + [Crk_C3G] → [Crk_C3G_pFRS2_pTrkA];   {Crk_C3G} , {pFRS2_pTrkA} , {Crk_C3G_pFRS2_pTrkA}
 
 R67 [pFRS2_pTrkA_endo] + [Crk_C3G] → [Crk_C3G_pFRS2_pTrkA_endo];   {Crk_C3G} , {pFRS2_pTrkA_endo} , {Crk_C3G_pFRS2_pTrkA_endo}
 
 R68 [pFRS2] → [FRS2];   {pFRS2}
 
 R69 [Rap1_GTP] → [Rap1_GDP];   {Rap1_GTP}
 
 R70 [Rap1_GDP] + [Crk_C3G_pFRS2_pTrkA_endo] → [Rap1_GTP] + [Crk_C3G_pFRS2_pTrkA_endo];   {Crk_C3G_pFRS2_pTrkA_endo} , {Rap1_GDP}
 
 R71 [Rap1_GTP] → [Rap1_GDP];   {Rap1_GTP}
 
 R72 [B_Raf_Rap1_GTP] → [B_Raf] + [Rap1_GDP];   {B_Raf_Rap1_GTP}
 
 R73 [Ras_GTP] + [c_Raf] → [c_Raf_Ras_GTP];   {c_Raf} , {Ras_GTP} , {c_Raf_Ras_GTP}
 
 R74 [Ras_GTP] + [B_Raf] → [B_Raf_Ras_GTP];   {B_Raf} , {Ras_GTP} , {B_Raf_Ras_GTP}
 
 R75 [B_Raf] + [Rap1_GTP] → [B_Raf_Rap1_GTP];   {B_Raf} , {Rap1_GTP} , {B_Raf_Rap1_GTP}
 
 R76 [ppMEKcyt_ERKcyt] → [ppMEKcyt] + [ppERKcyt];   {ppMEKcyt_ERKcyt}
 
 R77 2.0 × [ppERKcyt] → [dppERKcyt];   {ppERKcyt} , {dppERKcyt}
 
 R78 [MEKcyt] + [ERKcyt] → [MEKcyt_ERKcyt];   {MEKcyt} , {ERKcyt} , {MEKcyt_ERKcyt}
 
 R79 [ERKcyt] + [pMEKcyt] → [pMEKcyt_ERKcyt];   {pMEKcyt} , {ERKcyt} , {pMEKcyt_ERKcyt}
 
 R80 [ppMEKcyt] + [ERKcyt] → [ppMEKcyt_ERKcyt];   {ppMEKcyt} , {ERKcyt} , {ppMEKcyt_ERKcyt}
 
 R81 [MEKcyt] + [c_Raf_Ras_GTP] → [pMEKcyt] + [c_Raf_Ras_GTP];   {c_Raf_Ras_GTP} , {MEKcyt}
 
 R82 [pMEKcyt] + [c_Raf_Ras_GTP] → [ppMEKcyt] + [c_Raf_Ras_GTP];   {c_Raf_Ras_GTP} , {pMEKcyt}
 
 R83 [MEKcyt_ERKcyt] + [c_Raf_Ras_GTP] → [pMEKcyt_ERKcyt] + [c_Raf_Ras_GTP];   {c_Raf_Ras_GTP} , {MEKcyt_ERKcyt}
 
 R84 [pMEKcyt_ERKcyt] + [c_Raf_Ras_GTP] → [ppMEKcyt_ERKcyt] + [c_Raf_Ras_GTP];   {c_Raf_Ras_GTP} , {pMEKcyt_ERKcyt}
 
 R85 [MEKcyt] + [B_Raf_Ras_GTP] → [pMEKcyt] + [B_Raf_Ras_GTP];   {B_Raf_Ras_GTP} , {MEKcyt}
 
 R86 [pMEKcyt] + [B_Raf_Ras_GTP] → [ppMEKcyt] + [B_Raf_Ras_GTP];   {B_Raf_Ras_GTP} , {pMEKcyt}
 
 R87 [MEKcyt_ERKcyt] + [B_Raf_Ras_GTP] → [pMEKcyt_ERKcyt] + [B_Raf_Ras_GTP];   {B_Raf_Ras_GTP} , {MEKcyt_ERKcyt}
 
 R88 [pMEKcyt_ERKcyt] + [B_Raf_Ras_GTP] → [ppMEKcyt_ERKcyt] + [B_Raf_Ras_GTP];   {B_Raf_Ras_GTP} , {pMEKcyt_ERKcyt}
 
 R89 [MEKcyt] + [B_Raf_Rap1_GTP] → [pMEKcyt] + [B_Raf_Rap1_GTP];   {B_Raf_Rap1_GTP} , {MEKcyt}
 
 R90 [pMEKcyt] + [B_Raf_Rap1_GTP] → [ppMEKcyt] + [B_Raf_Rap1_GTP];   {B_Raf_Rap1_GTP} , {pMEKcyt}
 
 R91 [MEKcyt_ERKcyt] + [B_Raf_Rap1_GTP] → [pMEKcyt_ERKcyt] + [B_Raf_Rap1_GTP];   {B_Raf_Rap1_GTP} , {MEKcyt_ERKcyt}
 
 R92 [pMEKcyt_ERKcyt] + [B_Raf_Rap1_GTP] → [ppMEKcyt_ERKcyt] + [B_Raf_Rap1_GTP];   {B_Raf_Rap1_GTP} , {pMEKcyt_ERKcyt}
 
 R93 [pMEKcyt] → [MEKcyt];   {pMEKcyt}
 
 R94 [ppMEKcyt] → [pMEKcyt];   {ppMEKcyt}
 
 R95 [pMEKcyt_ERKcyt] → [MEKcyt_ERKcyt];   {pMEKcyt_ERKcyt}
 
 R96 [ppMEKcyt_ERKcyt] → [pMEKcyt_ERKcyt];   {ppMEKcyt_ERKcyt}
 
 R97 [ppERKcyt] → [ERKcyt];   {ppERKcyt}
 
 R98 [dppERKcyt] → [ppERKcyt] + [ERKcyt];   {dppERKcyt}
 
 R99 [ppMEKnuc_ERKnuc] → [ppMEKnuc] + [ppERKnuc];   {ppMEKnuc_ERKnuc}
 
 R100 2.0 × [ppERKnuc] → [dppERKnuc];   {ppERKnuc} , {dppERKnuc}
 
 R101 [MEKnuc] + [ERKnuc] → [MEKnuc_ERKnuc];   {MEKnuc} , {ERKnuc} , {MEKnuc_ERKnuc}
 
 R102 [ERKnuc] + [pMEKnuc] → [pMEKnuc_ERKnuc];   {pMEKnuc} , {ERKnuc} , {pMEKnuc_ERKnuc}
 
 R103 [ppMEKnuc] + [ERKnuc] → [ppMEKnuc_ERKnuc];   {ppMEKnuc} , {ERKnuc} , {ppMEKnuc_ERKnuc}
 
 R104 [pMEKnuc] → [MEKnuc];   {pMEKnuc}
 
 R105 [ppMEKnuc] → [pMEKnuc];   {ppMEKnuc}
 
 R106 [pMEKnuc_ERKnuc] → [MEKnuc_ERKnuc];   {pMEKnuc_ERKnuc}
 
 R107 [ppMEKnuc_ERKnuc] → [pMEKnuc_ERKnuc];   {ppMEKnuc_ERKnuc}
 
 R108 [ppERKnuc] → [ERKnuc];   {ppERKnuc}
 
 R109 [dppERKnuc] → [ppERKnuc] + [ERKnuc];   {dppERKnuc}
 
 R110 [pMEKcyt] → ;   {pMEKcyt}
 
 R111 [pMEKcyt] → [pMEKnuc] + [pMEKcyt];   {pMEKcyt}
 
 R112 [pMEKnuc] → [pMEKcyt] + [pMEKnuc];   {pMEKnuc}
 
 R113 [pMEKnuc] → ;   {pMEKnuc}
 
 R114 [MEKcyt_ERKcyt] → ;   {MEKcyt_ERKcyt}
 
 R115 [MEKcyt_ERKcyt] → [MEKnuc_ERKnuc] + [MEKcyt_ERKcyt];   {MEKcyt_ERKcyt}
 
 R116 [MEKnuc_ERKnuc] → [MEKcyt_ERKcyt] + [MEKnuc_ERKnuc];   {MEKnuc_ERKnuc}
 
 R117 [MEKnuc_ERKnuc] → ;   {MEKnuc_ERKnuc}
 
 R118 [ERKcyt] → ;   {ERKcyt}
 
 R119 [ERKcyt] → [ERKnuc] + [ERKcyt];   {ERKcyt}
 
 R120 [ERKnuc] → [ERKcyt] + [ERKnuc];   {ERKnuc}
 
 R121 [ERKnuc] → ;   {ERKnuc}
 
 R122 [MEKcyt] → ;   {MEKcyt}
 
 R123 [MEKcyt] → [MEKnuc] + [MEKcyt];   {MEKcyt}
 
 R124 [MEKnuc] → [MEKcyt] + [MEKnuc];   {MEKnuc}
 
 R125 [MEKnuc] → ;   {MEKnuc}
 
 R126 [ppERKcyt] → ;   {ppERKcyt}
 
 R127 [ppERKcyt] → [ppERKnuc] + [ppERKcyt];   {ppERKcyt}
 
 R128 [ppERKnuc] → [ppERKcyt] + [ppERKnuc];   {ppERKnuc}
 
 R129 [ppERKnuc] → ;   {ppERKnuc}
 
 R130 [ppMEKcyt] → ;   {ppMEKcyt}
 
 R131 [ppMEKcyt] → [ppMEKnuc] + [ppMEKcyt];   {ppMEKcyt}
 
 R132 [ppMEKnuc] → [ppMEKcyt] + [ppMEKnuc];   {ppMEKnuc}
 
 R133 [ppMEKnuc] → ;   {ppMEKnuc}
 
 R134 [ppMEKcyt_ERKcyt] → ;   {ppMEKcyt_ERKcyt}
 
 R135 [ppMEKcyt_ERKcyt] → [ppMEKnuc_ERKnuc] + [ppMEKcyt_ERKcyt];   {ppMEKcyt_ERKcyt}
 
 R136 [ppMEKnuc_ERKnuc] → [ppMEKcyt_ERKcyt] + [ppMEKnuc_ERKnuc];   {ppMEKnuc_ERKnuc}
 
 R137 [ppMEKnuc_ERKnuc] → ;   {ppMEKnuc_ERKnuc}
 
 R138 [dppERKcyt] → ;   {dppERKcyt}
 
 R139 [dppERKcyt] → [dppERKnuc] + [dppERKcyt];   {dppERKcyt}
 
 R140 [dppERKnuc] → [dppERKcyt] + [dppERKnuc];   {dppERKnuc}
 
 R141 [dppERKnuc] → ;   {dppERKnuc}
 
 R142 [pMEKcyt_ERKcyt] → ;   {pMEKcyt_ERKcyt}
 
 R143 [pMEKcyt_ERKcyt] → [pMEKnuc_ERKnuc] + [pMEKcyt_ERKcyt];   {pMEKcyt_ERKcyt}
 
 R144 [pMEKnuc_ERKnuc] → [pMEKcyt_ERKcyt] + [pMEKnuc_ERKnuc];   {pMEKnuc_ERKnuc}
 
 R145 [pMEKnuc_ERKnuc] → ;   {pMEKnuc_ERKnuc}
 
 reaction_1 [source] → [NGF];   {source}
 
 reaction_2 [NGF] → [NGFdeg];   {NGF}
 
 reaction_3 [NGFR_interstitial_fluid] + [NGF] ↔ [NGFR_L_interstitial_fluid];   {NGFR_interstitial_fluid} , {NGF} , {NGFR_L_interstitial_fluid}
 
 reaction_4 [NGF] + [tanezumab] ↔ [NGF_tanezumab];   {NGF} , {tanezumab} , {NGF_tanezumab}
 
 reaction_5 [tanezumab] → [tz_deg];   {tanezumab}
 
 reaction_6 [trkaI] → [trkaI_deg];   {trkaI}
 
 reaction_7 [trkaI] ↔ [trkaI_int];   {trkaI} , {trkaI_int}
 
 reaction_8 [NGFR_L_interstitial_fluid] ↔ [L_NGFR];   {NGFR_L_interstitial_fluid} , {L_NGFR}
 
 Intercomp mass transfer [NGFR] ↔ [NGFR_interstitial_fluid];   {NGFR} , {NGFR_interstitial_fluid}
 
 reaction_9 [L_NGFR] + [trkaI_int] ↔ [L_NGFR_I];   {L_NGFR} , {trkaI_int} , {L_NGFR_I}
 
 reaction_10 [trkaI_int] + [NGFR] ↔ [NGFR_I];   {trkaI_int} , {NGFR} , {NGFR_I}
 
 reaction_14 [NGFR_I] → [NGFR_I_deg];   {NGFR_I}
 
 reaction_15 [L_NGFR_I] → [L_NGFR_I_deg];   {L_NGFR_I}
 
   Neuron Spatial dimensions: 3.0  Compartment size: 0.001  (Units: liter)
 
 NGFR
Compartment: Neuron
Initial concentration: 0.06189368  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 L_NGFR
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pTrkA
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pTrkA_endo
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Shc_pTrkA
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Shc_pTrkA_endo
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pShc_pTrkA
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pShc_pTrkA_endo
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Grb2_SOS_pShc_pTrkA
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Grb2_SOS_pShc_pTrkA_endo
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 FRS2_pTrkA
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 FRS2_pTrkA_endo
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pFRS2_pTrkA
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pFRS2_pTrkA_endo
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Crk_C3G_pFRS2_pTrkA
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Crk_C3G_pFRS2_pTrkA_endo
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Shc
Compartment: Neuron
Initial concentration: 1.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Grb2_SOS_pShc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 FRS2
Compartment: Neuron
Initial concentration: 1.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Crk_C3G
Compartment: Neuron
Initial concentration: 0.4980158  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Dok
Compartment: Neuron
Initial concentration: 0.2993032  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pDok
Compartment: Neuron
Initial concentration: 6.12296E-4  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Grb2
Compartment: Neuron
Initial concentration: 0.9373994  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 SOS
Compartment: Neuron
Initial concentration: 0.03739938  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Grb2_SOS
Compartment: Neuron
Initial concentration: 0.06260062  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Ras_GTP
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Ras_GDP
Compartment: Neuron
Initial concentration: 0.1  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 B_Raf_Ras_GTP
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 B_Raf
Compartment: Neuron
Initial concentration: 0.2  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 c_Raf
Compartment: Neuron
Initial concentration: 0.5  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Rap1_GTP
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ppMEKcyt_ERKcyt
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ppMEKcyt
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ppERKcyt
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 dppERKcyt
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 MEKcyt
Compartment: Neuron
Initial concentration: 0.1469897  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ERKcyt
Compartment: Neuron
Initial concentration: 0.02803697  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 MEKcyt_ERKcyt
Compartment: Neuron
Initial concentration: 0.1121076  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pMEKcyt
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pMEKcyt_ERKcyt
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ppMEKnuc_ERKnuc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ppMEKnuc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ppERKnuc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 dppERKnuc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 MEKnuc
Compartment: Neuron
Initial concentration: 1.941234  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 ERKnuc
Compartment: Neuron
Initial concentration: 0.01599799  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 MEKnuc_ERKnuc
Compartment: Neuron
Initial concentration: 0.8432791  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pMEKnuc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pMEKnuc_ERKnuc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 c_Raf_Ras_GTP
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 B_Raf_Rap1_GTP
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Rap1_GDP
Compartment: Neuron
Initial concentration: 0.2  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Crk
Compartment: Neuron
Initial concentration: 0.5019842  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 C3G
Compartment: Neuron
Initial concentration: 0.001984189  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pDok_RasGAP
Compartment: Neuron
Initial concentration: 8.45291E-5  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 RasGAP
Compartment: Neuron
Initial concentration: 0.09991547  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 Grb2_pSOS
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pShc
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pSOS
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pFRS2
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 trkaI_int
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 pro_TrkA
Compartment: Neuron
Initial concentration: 0.020631  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
Constant
 
 L_NGFR_I
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 NGFR_I
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 NGFR_I_deg
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 L_NGFR_I_deg
Compartment: Neuron
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
   Interstitial fluid Spatial dimensions: 3.0  Compartment size: 12.0  (Units: liter)
 
 NGFR_interstitial_fluid
Compartment: Interstitial fluid
Initial concentration: 5.0E-6  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 source
Compartment: Interstitial fluid
Initial concentration: 1.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 NGF
Compartment: Interstitial fluid
Initial concentration: 3.0E-5  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 NGFdeg
Compartment: Interstitial fluid
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 NGFR_L_interstitial_fluid
Compartment: Interstitial fluid
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 tanezumab
Compartment: Interstitial fluid
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 NGF_tanezumab
Compartment: Interstitial fluid
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 tz_deg
Compartment: Interstitial fluid
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 trkaI
Compartment: Interstitial fluid
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
 trkaI_deg
Compartment: Interstitial fluid
Initial concentration: 0.0  (Units: MWBUILTINPREFIX_micro_MWBUILTINUNIT_mole)
 
Global Parameters (222)
 
   Km_104
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_105
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_106
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_107
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_108
Value: 0.02   (Units: micromolarity)
Constant
 
   Km_109
Value: 0.02   (Units: micromolarity)
Constant
 
   Km_39
Value: 0.1   (Units: micromolarity)
Constant
 
   Km_40
Value: 0.1   (Units: micromolarity)
Constant
 
   Km_41
Value: 0.1   (Units: micromolarity)
Constant
 
   Km_42
Value: 0.1   (Units: micromolarity)
Constant
 
   Km_43
Value: 0.1   (Units: micromolarity)
Constant
 
   Km_44
Value: 0.1   (Units: micromolarity)
Constant
 
   Km_45
Value: 0.1   (Units: micromolarity)
Constant
 
   Km_58
Value: 0.02   (Units: micromolarity)
Constant
 
   Km_59
Value: 25.641   (Units: micromolarity)
Constant
 
   Km_60
Value: 25.641   (Units: micromolarity)
Constant
 
   Km_61
Value: 25.641   (Units: micromolarity)
Constant
 
   Km_62
Value: 1.0   (Units: micromolarity)
Constant
 
   Km_63
Value: 1.0   (Units: micromolarity)
Constant
 
   Km_64
Value: 1.0   (Units: micromolarity)
Constant
 
   Km_70
Value: 0.01   (Units: micromolarity)
Constant
 
   Km_71
Value: 1.0   (Units: micromolarity)
Constant
 
   Km_72
Value: 1.0   (Units: micromolarity)
Constant
 
   Km_81
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_82
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_83
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_84
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_85
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_86
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_87
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_88
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_89
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_90
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_91
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_92
Value: 0.16   (Units: micromolarity)
Constant
 
   Km_93
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_94
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_95
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_96
Value: 15.657   (Units: micromolarity)
Constant
 
   Km_97
Value: 0.02   (Units: micromolarity)
Constant
 
   Km_98
Value: 0.02   (Units: micromolarity)
Constant
 
   MKP3cyt
Value: 0.018   (Units: micromolarity)
Constant
 
   MKP3nuc
Value: 0.006   (Units: micromolarity)
Constant
 
   PP2Acyt
Value: 0.24   (Units: micromolarity)
Constant
 
   PP2Anuc
Value: 0.08   (Units: micromolarity)
Constant
 
   Rap1GAP
Value: 0.012   (Units: micromolarity)
Constant
 
   Vmax_104
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_105
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_106
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_107
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_108
Value: 3.6   (Units: 1/minute)
Constant
 
   Vmax_109
Value: 3.6   (Units: 1/minute)
Constant
 
   Vmax_39
Value: 1.2   (Units: 1/minute)
Constant
 
   Vmax_40
Value: 1.2   (Units: 1/minute)
Constant
 
   Vmax_41
Value: 1.2   (Units: 1/minute)
Constant
 
   Vmax_42
Value: 1.2   (Units: 1/minute)
Constant
 
   Vmax_43
Value: 1.2   (Units: 1/minute)
Constant
 
   Vmax_44
Value: 1.2   (Units: 1/minute)
Constant
 
   Vmax_45
Value: 1.2   (Units: 1/minute)
Constant
 
   Vmax_58
Value: 120.0   (Units: 1/minute)
Constant
 
   Vmax_59
Value: 60.0   (Units: 1/minute)
Constant
 
   Vmax_60
Value: 60.0   (Units: 1/minute)
Constant
 
   Vmax_61
Value: 60.0   (Units: 1/minute)
Constant
 
   Vmax_62
Value: 600.0   (Units: 1/minute)
Constant
 
   Vmax_63
Value: 600.0   (Units: 1/minute)
Constant
 
   Vmax_64
Value: 600.0   (Units: 1/minute)
Constant
 
   Vmax_70
Value: 2.88   (Units: 1/minute)
Constant
 
   Vmax_71
Value: 120.0   (Units: 1/minute)
Constant
 
   Vmax_72
Value: 120.0   (Units: 1/minute)
Constant
 
   Vmax_81
Value: 30.0   (Units: 1/minute)
Constant
 
   Vmax_82
Value: 30.0   (Units: 1/minute)
Constant
 
   Vmax_83
Value: 30.0   (Units: 1/minute)
Constant
 
   Vmax_84
Value: 30.0   (Units: 1/minute)
Constant
 
   Vmax_85
Value: 12.0   (Units: 1/minute)
Constant
 
   Vmax_86
Value: 12.0   (Units: 1/minute)
Constant
 
   Vmax_87
Value: 12.0   (Units: 1/minute)
Constant
 
   Vmax_88
Value: 12.0   (Units: 1/minute)
Constant
 
   Vmax_89
Value: 18.0   (Units: 1/minute)
Constant
 
   Vmax_90
Value: 18.0   (Units: 1/minute)
Constant
 
   Vmax_91
Value: 18.0   (Units: 1/minute)
Constant
 
   Vmax_92
Value: 18.0   (Units: 1/minute)
Constant
 
   Vmax_93
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_94
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_95
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_96
Value: 180.0   (Units: 1/minute)
Constant
 
   Vmax_97
Value: 3.6   (Units: 1/minute)
Constant
 
   Vmax_98
Value: 3.6   (Units: 1/minute)
Constant
 
   kb_1
Value: 0.0166668   (Units: 1/minute)
Constant
 
   kb_100
Value: 4.5   (Units: 1/minute)
Constant
 
   kb_101
Value: 36.0   (Units: 1/minute)
Constant
 
   kb_102
Value: 36.0   (Units: 1/minute)
Constant
 
   kb_103
Value: 36.0   (Units: 1/minute)
Constant
 
   kb_18
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_19
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_20
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_21
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_22
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_23
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_24
Value: 6.0   (Units: 1/minute)
Constant
 
   kb_25
Value: 6.0   (Units: 1/minute)
Constant
 
   kb_26
Value: 6.0   (Units: 1/minute)
Constant
 
   kb_27
Value: 6.0   (Units: 1/minute)
Constant
 
   kb_46
Value: 1.008   (Units: 1/minute)
Constant
 
   kb_47
Value: 1.008   (Units: 1/minute)
Constant
 
   kb_48
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_49
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_50
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_55
Value: 1.99999998   (Units: 1/minute)
Constant
 
   kb_56
Value: 6.0E-4   (Units: 1/minute)
Constant
 
   kb_65
Value: 0.12   (Units: 1/minute)
Constant
 
   kb_66
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_67
Value: 12.0   (Units: 1/minute)
Constant
 
   kb_73
Value: 30.0   (Units: 1/minute)
Constant
 
   kb_74
Value: 30.0   (Units: 1/minute)
Constant
 
   kb_75
Value: 30.0   (Units: 1/minute)
Constant
 
   kb_77
Value: 4.5   (Units: 1/minute)
Constant
 
   kb_78
Value: 36.0   (Units: 1/minute)
Constant
 
   kb_79
Value: 36.0   (Units: 1/minute)
Constant
 
   kb_80
Value: 36.0   (Units: 1/minute)
Constant
 
   kf_1
Value: 0.049998   (Units: 1/minute)
Constant
 
   kf_10
Value: 0.0378   (Units: 1/minute)
Constant
 
   kf_100
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_101
Value: 978.24   (Units: 1/(micromolarity*minute))
Constant
 
   kf_102
Value: 978.24   (Units: 1/(micromolarity*minute))
Constant
 
   kf_103
Value: 978.24   (Units: 1/(micromolarity*minute))
Constant
 
   kf_11
Value: 0.0252   (Units: 1/minute)
Constant
 
   kf_110
Value: 6.48   (Units: 1/minute)
Constant
 
   kf_111
Value: 32.4   (Units: 1/minute)
Constant
 
   kf_112
Value: 0.48   (Units: 1/minute)
Constant
 
   kf_113
Value: 2.4   (Units: 1/minute)
Constant
 
   kf_114
Value: 3.12   (Units: 1/minute)
Constant
 
   kf_115
Value: 15.6   (Units: 1/minute)
Constant
 
   kf_116
Value: 0.42   (Units: 1/minute)
Constant
 
   kf_117
Value: 2.1   (Units: 1/minute)
Constant
 
   kf_118
Value: 0.216   (Units: 1/minute)
Constant
 
   kf_119
Value: 1.08   (Units: 1/minute)
Constant
 
   kf_12
Value: 0.0252   (Units: 1/minute)
Constant
 
   kf_120
Value: 0.1032   (Units: 1/minute)
Constant
 
   kf_121
Value: 0.516   (Units: 1/minute)
Constant
 
   kf_122
Value: 7.32   (Units: 1/minute)
Constant
 
   kf_123
Value: 36.6   (Units: 1/minute)
Constant
 
   kf_124
Value: 0.552   (Units: 1/minute)
Constant
 
   kf_125
Value: 2.76   (Units: 1/minute)
Constant
 
   kf_126
Value: 0.156   (Units: 1/minute)
Constant
 
   kf_127
Value: 0.78   (Units: 1/minute)
Constant
 
   kf_128
Value: 0.084   (Units: 1/minute)
Constant
 
   kf_129
Value: 0.42   (Units: 1/minute)
Constant
 
   kf_13
Value: 0.0252   (Units: 1/minute)
Constant
 
   kf_130
Value: 6.48   (Units: 1/minute)
Constant
 
   kf_131
Value: 32.4   (Units: 1/minute)
Constant
 
   kf_132
Value: 0.48   (Units: 1/minute)
Constant
 
   kf_133
Value: 2.4   (Units: 1/minute)
Constant
 
   kf_134
Value: 3.12   (Units: 1/minute)
Constant
 
   kf_135
Value: 15.6   (Units: 1/minute)
Constant
 
   kf_136
Value: 0.42   (Units: 1/minute)
Constant
 
   kf_137
Value: 2.1   (Units: 1/minute)
Constant
 
   kf_138
Value: 0.156   (Units: 1/minute)
Constant
 
   kf_139
Value: 0.78   (Units: 1/minute)
Constant
 
   kf_14
Value: 0.0252   (Units: 1/minute)
Constant
 
   kf_140
Value: 0.084   (Units: 1/minute)
Constant
 
   kf_141
Value: 0.42   (Units: 1/minute)
Constant
 
   kf_142
Value: 3.12   (Units: 1/minute)
Constant
 
   kf_143
Value: 15.6   (Units: 1/minute)
Constant
 
   kf_144
Value: 0.42   (Units: 1/minute)
Constant
 
   kf_145
Value: 2.1   (Units: 1/minute)
Constant
 
   kf_15
Value: 0.0252   (Units: 1/minute)
Constant
 
   kf_16
Value: 0.0252   (Units: 1/minute)
Constant
 
   kf_17
Value: 0.0252   (Units: 1/minute)
Constant
 
   kf_19
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_20
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_21
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_22
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_23
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_24
Value: 300.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_25
Value: 300.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_26
Value: 300.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_27
Value: 300.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_28
Value: 6.0   (Units: 1/minute)
Constant
 
   kf_29
Value: 6.0   (Units: 1/minute)
Constant
 
   kf_3
Value: 60.0   (Units: 1/minute)
Constant
 
   kf_30
Value: 120.0   (Units: 1/minute)
Constant
 
   kf_31
Value: 120.0   (Units: 1/minute)
Constant
 
   kf_32
Value: 0.132   (Units: 1/minute)
Constant
 
   kf_33
Value: 0.132   (Units: 1/minute)
Constant
 
   kf_34
Value: 0.132   (Units: 1/minute)
Constant
 
   kf_35
Value: 0.132   (Units: 1/minute)
Constant
 
   kf_36
Value: 0.132   (Units: 1/minute)
Constant
 
   kf_37
Value: 0.132   (Units: 1/minute)
Constant
 
   kf_38
Value: 0.132   (Units: 1/minute)
Constant
 
   kf_4
Value: 0.0378   (Units: 1/minute)
Constant
 
   kf_46
Value: 1.8   (Units: 1/(micromolarity*minute))
Constant
 
   kf_47
Value: 1.8   (Units: 1/(micromolarity*minute))
Constant
 
   kf_48
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_49
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_5
Value: 0.0378   (Units: 1/minute)
Constant
 
   kf_50
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_51
Value: 0.3   (Units: 1/minute)
Constant
 
   kf_52
Value: 0.3   (Units: 1/minute)
Constant
 
   kf_53
Value: 0.12   (Units: 1/minute)
Constant
 
   kf_54
Value: 0.12   (Units: 1/minute)
Constant
 
   kf_55
Value: 3.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_56
Value: 0.12   (Units: 1/minute)
Constant
 
   kf_57
Value: 0.0070002   (Units: 1/minute)
Constant
 
   kf_6
Value: 0.0378   (Units: 1/minute)
Constant
 
   kf_65
Value: 60.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_66
Value: 60.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_67
Value: 60.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_68
Value: 0.3   (Units: 1/minute)
Constant
 
   kf_69
Value: 0.006996   (Units: 1/minute)
Constant
 
   kf_7
Value: 0.0378   (Units: 1/minute)
Constant
 
   kf_73
Value: 3600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_74
Value: 3600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_75
Value: 3600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_76
Value: 9.0   (Units: 1/minute)
Constant
 
   kf_77
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
   kf_78
Value: 978.24   (Units: 1/(micromolarity*minute))
Constant
 
   kf_79
Value: 978.24   (Units: 1/(micromolarity*minute))
Constant
 
   kf_8
Value: 0.0378   (Units: 1/minute)
Constant
 
   kf_80
Value: 978.24   (Units: 1/(micromolarity*minute))
Constant
 
   kf_9
Value: 0.0378   (Units: 1/minute)
Constant
 
   kf_99
Value: 9.0   (Units: 1/minute)
Constant
 
   kf_18
Value: 600.0   (Units: 1/(micromolarity*minute))
Constant
 
reaction_1 (1)
 
   ksynthngf
Value: 3.849E-8   (Units: 1/minute)
Constant
 
reaction_2 (1)
 
   kdegnfg
Value: 0.001283   (Units: 1/minute)
Constant
 
reaction_3 (2)
 
   konngf
Value: 372.0   (Units: 1/(micromolarity*minute))
Constant
 
   koffngf
Value: 0.00384   (Units: 1/minute)
Constant
 
reaction_4 (2)
 
   kontz
Value: 16.2   (Units: 1/(micromolarity*minute))
Constant
 
   kofftz
Value: 1.8E-4   (Units: 1/minute)
Constant
 
reaction_5 (1)
 
   kdegtz
Value: 2.3E-5   (Units: 1/minute)
Constant
 
reaction_6 (1)
 
   kdegtrkaI
Value: 0.001925   (Units: 1/minute)
Constant
 
reaction_7 (2)
 
   ktrkaiin
Value: 83.33   (Units: 1/minute)
Constant
 
   ktrkaiout
Value: 1000000.0   (Units: 1/minute)
Constant
 
reaction_8 (2)
 
   ktranstngfrlout
Value: 2000.0   (Units: 1/minute)
Constant
 
   ktransngfrlin
Value: 2000.0   (Units: 1/minute)
Constant
 
Intercomp mass transfer (2)
 
   ktransinneuron
Value: 2000.0   (Units: 1/minute)
Constant
 
   ktransoutneuron
Value: 2000.0   (Units: 1/minute)
Constant
 
reaction_9 (2)
 
   kontrkaI
Value: 1.0E7   (Units: 1/(molarity*second))
Constant
 
   kofftrkaI
Value: 0.001   (Units: 1/second)
Constant
 
reaction_10 (2)
 
   kontrkaI
Value: 1.0E7   (Units: 1/(molarity*second))
Constant
 
   kofftrkaI
Value: 0.001   (Units: 1/second)
Constant
 
reaction_14 (1)
 
   kdegEI
Value: 0.0167   (Units: 1/minute)
Constant
 
reaction_15 (1)
 
   kdegEI
Value: 0.0167   (Units: 1/minute)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000588

Curator's comment: (updated: 29 Jan 2016 14:30:24 GMT)

Figure 4 - dppERKnuc response to NGF (solid line) is reproduced here using SimBiology Version 5.1, MATLAB Version 8.4 (R2014b).

Note: The SBML model was generated from SimBiology. The corresponding SimBiology project file (.sbproj) can be downloaded from the below link. Copasi do not generate appropriate simulation results for the following reasons, 1) "fast" reactions are not recognised, 2) Units definitions are not handled well.

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