Physiology

Reaction Diagram

reactionDiagram

Cross-References

Annotations

Reactions

Reactions
Name
Structure
Kinetics
Depiction
Raf1+GTP_RasRas_Raf1 Ras_Raf1_bind pm MassAction
Ras_BRaf+Ras_Raf1Ras_BRaf_Raf1_tetramer BRaf_Raf1_bind pm MassAction
Ras_BRaf_Raf1_tetramerRas_BRaf_pRaf1_tetramer BRaf_Raf1_phosph pm MassAction
Ras_pRaf1pRaf1+GTP_Ras Ras_pRaf1_unbind pm MassAction
BRaf+GTP_RasRas_BRaf Ras_BRaf_bind pm MassAction
Ras_pRaf1+Ras_Raf1Ras_pRaf1_Raf1_tetramer pRaf1_Raf1_bind pm MassAction
Ras_pRaf1_Raf1_tetramerRas_pRaf1_tetramer pRaf1_Raf1_phosph pm MassAction
sorafenib+Raf1iRaf1 sorafenib_Raf1_bind_cyt cytoplasm MassAction
iRaf1+GTP_RasRas_iRaf1 Ras_iRaf1_bind pm MassAction
Ras_iRaf1Ras_iRaf1_tetramer iRaf1_iRaf1_bind pm MassAction
Ras_BRaf+Ras_iRaf1Ras_Braf_iRaf1_tetramer BRaf_iRaf1_bind pm MassAction
pRaf1Raf1 pRaf1_dephosph cytoplasm MassAction
Ras_pRaf1_tetramerRas_pRaf1 pRaf1_pRaf1_unbind pm MassAction
Ras_BRaf_pRaf1_tetramerRas_BRaf+Ras_pRaf1 BRaf_pRaf1_unbind pm MassAction
sorafenib+BRafiBRaf sorafenib_BRaf_bind_cyt cytoplasm MassAction
MEKpMEK MEK_p cytoplasm MassAction
pMEKMEK MEK_dp cytoplasm MassAction
ERKpERK ERK_p cytoplasm MassAction
pERKERK ERK_dp cytoplasm MassAction
iBRafRas_iBRaf Ras_iBRaf_b pm MassAction
Ras_iBRafiBRaf_dimer iBRaf_dim pm MassAction
Ras_Raf1+Ras_iBRafRas_Raf1_iBRaf_tetramer iBRaf_Raf1_bind pm MassAction
Ras_Raf1_iBRaf_tetramerRas_pRaf1_iBRaf_tetramer Raf1_iBRaf_p pm MassAction
Ras_pRaf1_iBRaf_tetramerRas_iBRaf+Ras_pRaf1 pRaf1_iBRaf_ub pm MassAction
Ras_BRafBRaf_dimer BRaf_dim pm MassAction
Ras_pRaf1Ras_Raf1 Ras_pRaf1_dp pm MassAction
Ras_Raf1Ras_nfpRaf1 Ras_Raf1_nfp pm MassAction
Ras_nfpRaf1GTP_Ras+nfpRaf1 nfpRaf1_ub pm MassAction
nfpRaf1Raf1 nfpRaf1_dp cytoplasm MassAction
Ras_BRafRas_nfpBRaf BRaf_nfp pm MassAction
Ras_nfpBRafGTP_Ras+nfpBRaf nfpBRaf_ub pm MassAction
nfpBRafBRaf nfpBRaf_dp cytoplasm MassAction
Ras_iBRaf+Ras_BRafBRaf_iBRaf_dimer BRaf_iBRaf_dim pm MassAction
Ras_iRaf1Ras_nfpiRaf1 Ras_iRaf_nfp pm MassAction
Ras_nfpiRaf1nfpiRaf1+GTP_Ras nfpiRaf1_ub pm MassAction
nfpiRaf1iRaf1 nfpiRaf_dp cytoplasm MassAction
Ras_iBRafRas_nfpiBRaf Ras_iBRaf_nfp pm MassAction
Ras_nfpiBRafnfpiBRaf+GTP_Ras nfpiBRaf_ub pm MassAction
nfpiBRafiBRaf nfpiBRaf_dp cytoplasm MassAction
Ras_iRaf1+Ras_iBRafRas_iRaf1_iBRaf1_tetramer iRaf_iBRaf_dim pm MassAction

Structures

Name
Type
Electrical
pm Membrane (+)   (-)
cytoplasm Compartment (+)   (-)

Species

Name
Structure
BioNetGen Definition
Depiction
sorafenib cytoplasm cytoplasm
GTP_Ras pm pm
Raf1 cytoplasm cytoplasm
pRaf1 cytoplasm cytoplasm
Ras_Raf1 pm pm
Ras_iRaf1 pm pm
Ras_pRaf1_Raf1_tetramer pm pm
Ras_BRaf pm pm
Ras_pRaf1 pm pm
Ras_BRaf_Raf1_tetramer pm pm
Ras_iRaf1_tetramer pm pm
iRaf1 cytoplasm cytoplasm
BRaf cytoplasm cytoplasm
Ras_Braf_iRaf1_tetramer pm pm
Ras_pRaf1_tetramer pm pm
Ras_BRaf_pRaf1_tetramer pm pm
MEK cytoplasm cytoplasm
pMEK cytoplasm cytoplasm
ERK cytoplasm cytoplasm
iBRaf cytoplasm cytoplasm
Ras_Raf1_iBRaf_tetramer pm pm
Ras_pRaf1_iBRaf_tetramer pm pm
pERK cytoplasm cytoplasm
iBRaf_dimer pm pm
BRaf_dimer pm pm
Ras_iBRaf pm pm
Ras_nfpRaf1 pm pm
nfpRaf1 cytoplasm cytoplasm
Ras_nfpBRaf pm pm
nfpBRaf cytoplasm cytoplasm
BRaf_iBRaf_dimer pm pm
Ras_nfpiBRaf pm pm
nfpiBRaf cytoplasm cytoplasm
Ras_nfpiRaf1 pm pm
nfpiRaf1 cytoplasm cytoplasm
Ras_iRaf1_iBRaf1_tetramer pm pm

Molecules

Name
BioNetGen Definition
DEPICTION

Observables

Name
Structure
Count
BNGL Definition
Sequence Type
DEPICTION

Applications

Name
Properties Math Type
Annotation
-sorafenib Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental cloned from 'Raf-1 activation, -sorafenib' owned by user pmyers1995
+sorafenib Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental cloned from 'Raf-1 activation, +sorafenib' owned by user pmyers1995 (copied from Raf-1 activation, -sorafenib)
+sorafenib after 60 min EGF pretreatment Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental (copied from -sorafenib) cloned from 'Raf-1 activation, -sorafenib' owned by user pmyers1995
+sorafenib after 15 min EGF pretreatment Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental (copied from +sorafenib after 60 min EGF pretreatment) (copied from -sorafenib) cloned from 'Raf-1 activation, -sorafenib' owned by user pmyers1995
+sorafenib after 30 min EGF pretreatment Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental (copied from Copy of +sorafenib after 60 min EGF pretreatment) (copied from +sorafenib after 60 min EGF pretreatment) (copied from -sorafenib) cloned from 'Raf-1 activation, -sorafenib' owned by user pmyers1995
+sorafenib after 5 min EGF pretreatment Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental (copied from Copy of Copy of +sorafenib after 60 min EGF pretreatment) (copied from Copy of +sorafenib after 60 min EGF pretreatment) (copied from +sorafenib after 60 min EGF pretreatment) (copied from -sorafenib) cloned from 'Raf-1 activation, -sorafenib' owned by user pmyers1995
const. active Ras-GTP, -sorafenib Specs - Species
Specs - Reaction
Simulations
Deterministic (ODE) Compartmental (copied from -sorafenib) cloned from 'Raf-1 activation, -sorafenib' owned by user pmyers1995

Specifications (Species) - -sorafenib go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
sorafenib 0.0 [uM] 0.0 [um2/min] cytoplasm
Raf1 12000.0 [uM] 0.0 [um2/min] cytoplasm
pRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
iRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
BRaf 1000.0 [uM] 0.0 [um2/min] cytoplasm
MEK 500000.0 [uM] 0.0 [um2/min] cytoplasm
pMEK 0.0 [uM] 0.0 [um2/min] cytoplasm
ERK 600000.0 [uM] 0.0 [um2/min] cytoplasm
iBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
pERK 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
GTP_Ras ((A * t * exp(( - t / B))) + (C * t / (t + D))) [uM] 0.0 [um2/min] pm
Ras_Raf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Braf_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Raf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
BRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_iBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpBRaf 0.0 [uM] 0.0 [um2/min] pm
BRaf_iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_iBRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm

Specifications (Reaction) - -sorafenib go to Simulations

Name
Enabled?
Ras_Raf1_bind included
BRaf_Raf1_bind included
BRaf_Raf1_phosph included
Ras_pRaf1_unbind included
Ras_BRaf_bind included
pRaf1_Raf1_bind included
pRaf1_Raf1_phosph included
sorafenib_Raf1_bind_cyt excluded
Ras_iRaf1_bind excluded
iRaf1_iRaf1_bind excluded
BRaf_iRaf1_bind excluded
pRaf1_dephosph included
pRaf1_pRaf1_unbind included
BRaf_pRaf1_unbind included
sorafenib_BRaf_bind_cyt excluded
MEK_p included
MEK_dp included
ERK_p included
ERK_dp included
Ras_iBRaf_b excluded
iBRaf_dim excluded
iBRaf_Raf1_bind excluded
Raf1_iBRaf_p excluded
pRaf1_iBRaf_ub excluded
BRaf_dim included
Ras_pRaf1_dp included
Ras_Raf1_nfp included
nfpRaf1_ub included
nfpRaf1_dp included
BRaf_nfp included
nfpBRaf_ub included
nfpBRaf_dp included
BRaf_iBRaf_dim excluded
Ras_iRaf_nfp excluded
nfpiRaf1_ub excluded
nfpiRaf_dp excluded
Ras_iBRaf_nfp excluded
nfpiBRaf_ub excluded
nfpiBRaf_dp excluded
iRaf_iBRaf_dim excluded

Simulations - -sorafenib go to Specifications

Name
End Time
Output Options
60 min 60.0

KeepEvery 1

KeepAtMost 1000

Fitted binding rates 60.0

KeepEvery 1

KeepAtMost 1000

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial1069339151

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment pm

Events

Name Variable Rate Expression

Specifications (Species) - +sorafenib go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
sorafenib 10.0 [uM] 0.0 [um2/min] cytoplasm
Raf1 12000.0 [uM] 0.0 [um2/min] cytoplasm
pRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
iRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
BRaf 1000.0 [uM] 0.0 [um2/min] cytoplasm
MEK 500000.0 [uM] 0.0 [um2/min] cytoplasm
pMEK 0.0 [uM] 0.0 [um2/min] cytoplasm
ERK 600000.0 [uM] 0.0 [um2/min] cytoplasm
iBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
pERK 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
GTP_Ras ((As * t * exp(( - t / Bs))) + (Cs * t / (t + Ds))) [uM] 0.0 [um2/min] pm
Ras_Raf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Braf_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Raf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
BRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_iBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpBRaf 0.0 [uM] 0.0 [um2/min] pm
BRaf_iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_iBRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm

Specifications (Reaction) - +sorafenib go to Simulations

Name
Enabled?
Ras_Raf1_bind included
BRaf_Raf1_bind included
BRaf_Raf1_phosph included
Ras_pRaf1_unbind included
Ras_BRaf_bind included
pRaf1_Raf1_bind included
pRaf1_Raf1_phosph included
sorafenib_Raf1_bind_cyt included
Ras_iRaf1_bind included
iRaf1_iRaf1_bind included
BRaf_iRaf1_bind included
pRaf1_dephosph included
pRaf1_pRaf1_unbind included
BRaf_pRaf1_unbind included
sorafenib_BRaf_bind_cyt included
MEK_p included
MEK_dp included
ERK_p included
ERK_dp included
Ras_iBRaf_b included
iBRaf_dim included
iBRaf_Raf1_bind included
Raf1_iBRaf_p included
pRaf1_iBRaf_ub included
BRaf_dim included
Ras_pRaf1_dp included
Ras_Raf1_nfp included
nfpRaf1_ub included
nfpRaf1_dp included
BRaf_nfp included
nfpBRaf_ub included
nfpBRaf_dp included
BRaf_iBRaf_dim included
Ras_iRaf_nfp included
nfpiRaf1_ub included
nfpiRaf_dp included
Ras_iBRaf_nfp included
nfpiBRaf_ub included
nfpiBRaf_dp included
iRaf_iBRaf_dim included

Simulations - +sorafenib go to Specifications

Name
End Time
Output Options
Fitted binding 60.0

KeepEvery 1

KeepAtMost 1000

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial1102832951

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment pm

Events

Name Variable Rate Expression

Specifications (Species) - +sorafenib after 60 min EGF pretreatment go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
sorafenib (10.0 * (t > 60.0)) [uM] 0.0 [um2/min] cytoplasm
Raf1 12000.0 [uM] 0.0 [um2/min] cytoplasm
pRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
iRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
BRaf 1000.0 [uM] 0.0 [um2/min] cytoplasm
MEK 500000.0 [uM] 0.0 [um2/min] cytoplasm
pMEK 0.0 [uM] 0.0 [um2/min] cytoplasm
ERK 600000.0 [uM] 0.0 [um2/min] cytoplasm
iBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
pERK 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
GTP_Ras ((A * t * exp(( - t / B))) + (C * t / (t + D))) [uM] 0.0 [um2/min] pm
Ras_Raf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Braf_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Raf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
BRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_iBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpBRaf 0.0 [uM] 0.0 [um2/min] pm
BRaf_iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_iBRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm

Specifications (Reaction) - +sorafenib after 60 min EGF pretreatment go to Simulations

Name
Enabled?
Ras_Raf1_bind included
BRaf_Raf1_bind included
BRaf_Raf1_phosph included
Ras_pRaf1_unbind included
Ras_BRaf_bind included
pRaf1_Raf1_bind included
pRaf1_Raf1_phosph included
sorafenib_Raf1_bind_cyt included
Ras_iRaf1_bind included
iRaf1_iRaf1_bind included
BRaf_iRaf1_bind included
pRaf1_dephosph included
pRaf1_pRaf1_unbind included
BRaf_pRaf1_unbind included
sorafenib_BRaf_bind_cyt included
MEK_p included
MEK_dp included
ERK_p included
ERK_dp included
Ras_iBRaf_b included
iBRaf_dim included
iBRaf_Raf1_bind included
Raf1_iBRaf_p included
pRaf1_iBRaf_ub included
BRaf_dim included
Ras_pRaf1_dp included
Ras_Raf1_nfp included
nfpRaf1_ub included
nfpRaf1_dp included
BRaf_nfp included
nfpBRaf_ub included
nfpBRaf_dp included
BRaf_iBRaf_dim included
Ras_iRaf_nfp included
nfpiRaf1_ub included
nfpiRaf_dp included
Ras_iBRaf_nfp included
nfpiBRaf_ub included
nfpiBRaf_dp included
iRaf_iBRaf_dim included

Simulations - +sorafenib after 60 min EGF pretreatment go to Specifications

Name
End Time
Output Options
60 min EGF pretreat 80.0

KeepEvery 1

KeepAtMost 1000

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial1069339151

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment pm

Events

Name Variable Rate Expression

Specifications (Species) - +sorafenib after 15 min EGF pretreatment go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
sorafenib (10.0 * (t > 15.0)) [uM] 0.0 [um2/min] cytoplasm
Raf1 12000.0 [uM] 0.0 [um2/min] cytoplasm
pRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
iRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
BRaf 1000.0 [uM] 0.0 [um2/min] cytoplasm
MEK 500000.0 [uM] 0.0 [um2/min] cytoplasm
pMEK 0.0 [uM] 0.0 [um2/min] cytoplasm
ERK 600000.0 [uM] 0.0 [um2/min] cytoplasm
iBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
pERK 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
GTP_Ras ((A * t * exp(( - t / B))) + (C * t / (t + D))) [uM] 0.0 [um2/min] pm
Ras_Raf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Braf_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Raf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
BRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_iBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpBRaf 0.0 [uM] 0.0 [um2/min] pm
BRaf_iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_iBRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm

Specifications (Reaction) - +sorafenib after 15 min EGF pretreatment go to Simulations

Name
Enabled?
Ras_Raf1_bind included
BRaf_Raf1_bind included
BRaf_Raf1_phosph included
Ras_pRaf1_unbind included
Ras_BRaf_bind included
pRaf1_Raf1_bind included
pRaf1_Raf1_phosph included
sorafenib_Raf1_bind_cyt included
Ras_iRaf1_bind included
iRaf1_iRaf1_bind included
BRaf_iRaf1_bind included
pRaf1_dephosph included
pRaf1_pRaf1_unbind included
BRaf_pRaf1_unbind included
sorafenib_BRaf_bind_cyt included
MEK_p included
MEK_dp included
ERK_p included
ERK_dp included
Ras_iBRaf_b included
iBRaf_dim included
iBRaf_Raf1_bind included
Raf1_iBRaf_p included
pRaf1_iBRaf_ub included
BRaf_dim included
Ras_pRaf1_dp included
Ras_Raf1_nfp included
nfpRaf1_ub included
nfpRaf1_dp included
BRaf_nfp included
nfpBRaf_ub included
nfpBRaf_dp included
BRaf_iBRaf_dim included
Ras_iRaf_nfp included
nfpiRaf1_ub included
nfpiRaf_dp included
Ras_iBRaf_nfp included
nfpiBRaf_ub included
nfpiBRaf_dp included
iRaf_iBRaf_dim included

Simulations - +sorafenib after 15 min EGF pretreatment go to Specifications

Name
End Time
Output Options
15 min EGF pretreat 35.0

KeepEvery 1

KeepAtMost 1000

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial1069339151

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment pm

Events

Name Variable Rate Expression

Specifications (Species) - +sorafenib after 30 min EGF pretreatment go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
sorafenib (10.0 * (t > 30.0)) [uM] 0.0 [um2/min] cytoplasm
Raf1 12000.0 [uM] 0.0 [um2/min] cytoplasm
pRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
iRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
BRaf 1000.0 [uM] 0.0 [um2/min] cytoplasm
MEK 500000.0 [uM] 0.0 [um2/min] cytoplasm
pMEK 0.0 [uM] 0.0 [um2/min] cytoplasm
ERK 600000.0 [uM] 0.0 [um2/min] cytoplasm
iBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
pERK 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
GTP_Ras ((A * t * exp(( - t / B))) + (C * t / (t + D))) [uM] 0.0 [um2/min] pm
Ras_Raf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Braf_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Raf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
BRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_iBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpBRaf 0.0 [uM] 0.0 [um2/min] pm
BRaf_iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_iBRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm

Specifications (Reaction) - +sorafenib after 30 min EGF pretreatment go to Simulations

Name
Enabled?
Ras_Raf1_bind included
BRaf_Raf1_bind included
BRaf_Raf1_phosph included
Ras_pRaf1_unbind included
Ras_BRaf_bind included
pRaf1_Raf1_bind included
pRaf1_Raf1_phosph included
sorafenib_Raf1_bind_cyt included
Ras_iRaf1_bind included
iRaf1_iRaf1_bind included
BRaf_iRaf1_bind included
pRaf1_dephosph included
pRaf1_pRaf1_unbind included
BRaf_pRaf1_unbind included
sorafenib_BRaf_bind_cyt included
MEK_p included
MEK_dp included
ERK_p included
ERK_dp included
Ras_iBRaf_b included
iBRaf_dim included
iBRaf_Raf1_bind included
Raf1_iBRaf_p included
pRaf1_iBRaf_ub included
BRaf_dim included
Ras_pRaf1_dp included
Ras_Raf1_nfp included
nfpRaf1_ub included
nfpRaf1_dp included
BRaf_nfp included
nfpBRaf_ub included
nfpBRaf_dp included
BRaf_iBRaf_dim included
Ras_iRaf_nfp included
nfpiRaf1_ub included
nfpiRaf_dp included
Ras_iBRaf_nfp included
nfpiBRaf_ub included
nfpiBRaf_dp included
iRaf_iBRaf_dim included

Simulations - +sorafenib after 30 min EGF pretreatment go to Specifications

Name
End Time
Output Options
30 min EGF pretreat 50.0

KeepEvery 1

KeepAtMost 1000

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial1069339151

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment pm

Events

Name Variable Rate Expression

Specifications (Species) - +sorafenib after 5 min EGF pretreatment go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
sorafenib (10.0 * (t > 5.0)) [uM] 0.0 [um2/min] cytoplasm
Raf1 12000.0 [uM] 0.0 [um2/min] cytoplasm
pRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
iRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
BRaf 1000.0 [uM] 0.0 [um2/min] cytoplasm
MEK 500000.0 [uM] 0.0 [um2/min] cytoplasm
pMEK 0.0 [uM] 0.0 [um2/min] cytoplasm
ERK 600000.0 [uM] 0.0 [um2/min] cytoplasm
iBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
pERK 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
GTP_Ras ((A * t * exp(( - t / B))) + (C * t / (t + D))) [uM] 0.0 [um2/min] pm
Ras_Raf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Braf_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Raf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
BRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_iBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpBRaf 0.0 [uM] 0.0 [um2/min] pm
BRaf_iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_iBRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm

Specifications (Reaction) - +sorafenib after 5 min EGF pretreatment go to Simulations

Name
Enabled?
Ras_Raf1_bind included
BRaf_Raf1_bind included
BRaf_Raf1_phosph included
Ras_pRaf1_unbind included
Ras_BRaf_bind included
pRaf1_Raf1_bind included
pRaf1_Raf1_phosph included
sorafenib_Raf1_bind_cyt included
Ras_iRaf1_bind included
iRaf1_iRaf1_bind included
BRaf_iRaf1_bind included
pRaf1_dephosph included
pRaf1_pRaf1_unbind included
BRaf_pRaf1_unbind included
sorafenib_BRaf_bind_cyt included
MEK_p included
MEK_dp included
ERK_p included
ERK_dp included
Ras_iBRaf_b included
iBRaf_dim included
iBRaf_Raf1_bind included
Raf1_iBRaf_p included
pRaf1_iBRaf_ub included
BRaf_dim included
Ras_pRaf1_dp included
Ras_Raf1_nfp included
nfpRaf1_ub included
nfpRaf1_dp included
BRaf_nfp included
nfpBRaf_ub included
nfpBRaf_dp included
BRaf_iBRaf_dim included
Ras_iRaf_nfp included
nfpiRaf1_ub included
nfpiRaf_dp included
Ras_iBRaf_nfp included
nfpiBRaf_ub included
nfpiBRaf_dp included
iRaf_iBRaf_dim included

Simulations - +sorafenib after 5 min EGF pretreatment go to Specifications

Name
End Time
Output Options
5 min EGF pretreat 25.0

KeepEvery 1

KeepAtMost 1000

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial1069339151

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment pm

Events

Name Variable Rate Expression

Specifications (Species) - const. active Ras-GTP, -sorafenib go to Simulations

Species
Initial Condition
Diffusion Constant
Structure
sorafenib 0.0 [uM] 0.0 [um2/min] cytoplasm
Raf1 12000.0 [uM] 0.0 [um2/min] cytoplasm
pRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
iRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
BRaf 1000.0 [uM] 0.0 [um2/min] cytoplasm
MEK 500000.0 [uM] 0.0 [um2/min] cytoplasm
pMEK 0.0 [uM] 0.0 [um2/min] cytoplasm
ERK 600000.0 [uM] 0.0 [um2/min] cytoplasm
iBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
pERK 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiBRaf 0.0 [uM] 0.0 [um2/min] cytoplasm
nfpiRaf1 0.0 [uM] 0.0 [um2/min] cytoplasm
GTP_Ras 27000.0 [uM] 0.0 [um2/min] pm
Ras_Raf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_Raf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Braf_iRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_BRaf_pRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_Raf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
Ras_pRaf1_iBRaf_tetramer 0.0 [uM] 0.0 [um2/min] pm
iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
BRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_iBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpBRaf 0.0 [uM] 0.0 [um2/min] pm
BRaf_iBRaf_dimer 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiBRaf 0.0 [uM] 0.0 [um2/min] pm
Ras_nfpiRaf1 0.0 [uM] 0.0 [um2/min] pm
Ras_iRaf1_iBRaf1_tetramer 0.0 [uM] 0.0 [um2/min] pm

Specifications (Reaction) - const. active Ras-GTP, -sorafenib go to Simulations

Name
Enabled?
Ras_Raf1_bind included
BRaf_Raf1_bind included
BRaf_Raf1_phosph included
Ras_pRaf1_unbind included
Ras_BRaf_bind included
pRaf1_Raf1_bind included
pRaf1_Raf1_phosph included
sorafenib_Raf1_bind_cyt excluded
Ras_iRaf1_bind excluded
iRaf1_iRaf1_bind excluded
BRaf_iRaf1_bind excluded
pRaf1_dephosph included
pRaf1_pRaf1_unbind included
BRaf_pRaf1_unbind included
sorafenib_BRaf_bind_cyt included
MEK_p included
MEK_dp included
ERK_p included
ERK_dp included
Ras_iBRaf_b excluded
iBRaf_dim excluded
iBRaf_Raf1_bind excluded
Raf1_iBRaf_p excluded
pRaf1_iBRaf_ub excluded
BRaf_dim included
Ras_pRaf1_dp included
Ras_Raf1_nfp included
nfpRaf1_ub included
nfpRaf1_dp included
BRaf_nfp included
nfpBRaf_ub included
nfpBRaf_dp included
BRaf_iBRaf_dim excluded
Ras_iRaf_nfp excluded
nfpiRaf1_ub excluded
nfpiRaf_dp excluded
Ras_iBRaf_nfp excluded
nfpiBRaf_ub excluded
nfpiBRaf_dp excluded
iRaf_iBRaf_dim excluded

Simulations - const. active Ras-GTP, -sorafenib go to Specifications

Name
End Time
Output Options
Simulation0 60.0

KeepEvery 1

KeepAtMost 1000

10x Ras 60.0

KeepEvery 1

KeepAtMost 1000

Assignments

Name Variable Assignment Function Expression

Events

Name Trigger Type Variable Assignment

Geometry non-spatial757173534

(Origin: 0.0, 0.0, 0.0; Extent: 10.0, 10.0, 10.0 [um])

Dimension Type Subdomain Adjacent Subvolumes Size Mapped Compartment
Compartmental Compartment pm

Events

Name Variable Rate Expression

Global Parameters

Name
Expression
kSon 100000.0[uM-1.min-1]
kSoff 420.0[min-1]
kpR1 186.0[min-1]
kdR1f 0.0191[molecules-1.min-1]
kR1f 1.84E-7[molecules.min-1]
kR1r 0.212[min-1]
kBf 2.47E-7[min-1.molecules-1]
kBr 0.0367[min-1]
kdR1r 111.0[min-1]
kdpR1 0.6[min-1]
boundRaf_frac_parameter (Raf1_pm_param / (Raf1_cyt_param + Raf1_pm_param))[tbd]
A 20671.0[tbd]
B 3.6724[tbd]
C 6.7089E16[tbd]
RasGTP_parameter (GTP_Ras + (2.0 * (Ras_iRaf1_tetramer + Ras_Braf_iRaf1_tetramer + Ras_BRaf_Raf1_tetramer + Ras_pRaf1_Raf1_tetramer + Ras_BRaf_pRaf1_tetramer + Ras_pRaf1_tetramer + BRaf_dimer + BRaf_iBRaf_dimer + iBRaf_dimer + Ras_iRaf1_iBRaf1_tetramer + Ras_Raf1_iBRaf_tetramer + Ras_pRaf1_iBRaf_tetramer)) + Ras_BRaf + Ras_iRaf1 + Ras_pRaf1 + Ras_Raf1 + Ras_nfpRaf1 + Ras_nfpiRaf1 + Ras_iBRaf + Ras_nfpiBRaf + Ras_nfpBRaf)[tbd]
kiR1f 1.84E-7[min-1.molecules-1]
kiR1r 0.212[min-1]
Raf1_pm_param (Ras_pRaf1 + (2.0 * Ras_pRaf1_Raf1_tetramer) + Ras_BRaf_Raf1_tetramer + Ras_iRaf1 + Ras_Raf1 + (2.0 * Ras_iRaf1_tetramer) + Ras_Braf_iRaf1_tetramer + Ras_BRaf_pRaf1_tetramer + (2.0 * Ras_pRaf1_tetramer) + Ras_nfpiRaf1 + Ras_nfpRaf1 + Ras_iRaf1_iBRaf1_tetramer + Ras_Raf1_iBRaf_tetramer + Ras_pRaf1_iBRaf_tetramer)[tbd]
Raf1_cyt_param (Raf1 + pRaf1 + iRaf1 + nfpRaf1 + nfpiRaf1)[tbd]
kMEKp 6.0E-6[molecules-1.min-1]
active_Raf ((2.0 * BRaf_dimer) + Ras_BRaf_Raf1_tetramer + (2.0 * Ras_BRaf_pRaf1_tetramer) + Ras_pRaf1_iBRaf_tetramer + Ras_pRaf1 + Ras_pRaf1_Raf1_tetramer + (2.0 * Ras_pRaf1_tetramer) + pRaf1 + BRaf_iBRaf_dimer + Ras_Braf_iRaf1_tetramer)[tbd]
kERKp 6.0E-5[min-1.molecules-1]
kERKdp 0.6[min-1]
kMEKdp 0.6[min-1]
kiBf 2.47E-7[molecules-1.min-1]
kiBr 0.0367[min-1]
kfpR1r 2.12[min-1]
kfpBr 0.367[min-1]
knfpBR1 6.0E-7[min-1.molecules-1]
D 1.1735E15[tbd]
As 21930.665775907[tbd]
Bs 3.30082007598438[tbd]
Cs 5.37755813880742E16[tbd]
Ds 1.42262832362309E15[tbd]