131398
value: 0.1
name: k4
type: LocalParameter

COPASI7
reactant: 131578
type: Reaction
kinetic law: 131614
product: 131590
fast: false
reversible: false
modifier: 075238
name: 2
has version: GO:0016311
modifier: 075226
modifier: 131602

131050
has only substance units: false
boundary condition: false
in compartment: 130954
initial concentration: 0.0
is version of: P28482
constant: false
is version of: C00562
type: Species
initial amount: NaN
name: M_PP

BIOMD0000000441
time units: time
function def: 130882
name: function_4_7_1
function def: 130870
reaction: COPASI4
reaction: COPASI5
area units: area
name: function_4_4_1
compartment: 130954
reaction: COPASI2
species: 131050
name: function_4_1_1
substance units: 130930
name: function_4_2_1
species: 130978
name: Sarma2012 - Oscillations in MAPK cascade (S2)
reaction: COPASI11
name: function_4_9_1
species: 131014
species: 131074
is: GO:0000165
name: function_4_5_1
name: function_4_3_1
created:
  W3 CDTF: Mon Mar 18 12:10:14 GMT 2013
function def: 130894
species: 131086
units def: 130906
reaction: COPASI8
reaction: COPASI9
function def: 130858
species: 130990
species: 131038
is: http://identifiers.org/taxonomy/131567
function def: 130846
length unit: length
is described by: http://identifiers.org/pubmed/22694947
name: function_4_6_1
curated: true
is: MODEL1112190004
function def: 130834
modified:
  W3 CDTF: Fri Jun 07 12:45:28 BST 2013
name: function_4_8_1
volume units: 130906
species: 130966
function def: COPASI12
notes: Sarma2012 - Oscillations in MAPK cascade (S2) Two plausible designs (S1 and S2) of coupled positive and negative feedback loops of MAPK cascade has been described in this paper. This model corresponds to model S2 that comprises negative feedback from MK-PP to MKK_PP layer coupled to positive feedback from MK-PP to MKKK-P layer. This model is described in the article: Oscillations in MAPK cascade triggered by two distinct designs of coupled positive and negative feedback loops. Sarma U, Ghosh I. BMC Res Notes. 2012 Jun 13;5:287. Abstract: BACKGROUND: Feedback loops, both positive and negative are embedded in the Mitogen Activated Protein Kinase (MAPK) cascade. In the three layer MAPK cascade, both feedback loops originate from the terminal layer and their sites of action are either of the two upstream layers. Recent studies have shown that the cascade uses coupled positive and negative feedback loops in generating oscillations. Two plausible designs of coupled positive and negative feedback loops can be elucidated from the literature; in one design the positive feedback precedes the negative feedback in the direction of signal flow and vice-versa in another. But it remains unexplored how the two designs contribute towards triggering oscillations in MAPK cascade. Thus it is also not known how amplitude, frequency, robustness or nature (analogous/digital) of the oscillations would be shaped by these two designs. RESULTS: We built two models of MAPK cascade that exhibited oscillations as function of two underlying designs of coupled positive and negative feedback loops. Frequency, amplitude and nature (digital/analogous) of oscillations were found to be differentially determined by each design. It was observed that the positive feedback emerging from an oscillating MAPK cascade and functional in an external signal processing module can trigger oscillations in the target module, provided that the target module satisfy certain parametric requirements. The augmentation of …
function def: 130798
reaction: COPASI10
reaction: COPASI6
reaction: COPASI7
species: 131002
creator:
  ORG:
    orgname: National Centre for Cell Science
  n:
    given: Uddipan
    family: Sarma
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
species: 131062
function def: 130822
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Nick
    family: Juty
function def: 130810
name: function_4_10_1
units def: 130930
reaction: COPASI3
type: SBMLModel
species: 131026

131206
stoichiometry: 1.0
species: 131002
type: SpeciesReference

COPASI6
type: Reaction
reversible: false
product: 131506
fast: false
modifier: 131530
name: 8
modifier: 075190
modifier: 075214
modifier: 075202
modifier: 131518
kinetic law: 131542
is version of: GO:0016310
reactant: 131494

131182
value: 6.0
name: V1
type: LocalParameter

131506
stoichiometry: 1.0
species: 131050
type: SpeciesReference

130954
is: GO:0005623
constant: true
size: 1.0
spatial dimensions: 3.0
name: compartment
type: Compartment

131266
value: 20.0
name: K3
type: LocalParameter

131038
boundary condition: false
name: M_P
in compartment: 130954
has only substance units: false
initial amount: NaN
constant: false
type: Species
initial concentration: 0.0
is version of: P28482
is version of: C00562

131890
value: 20.0
name: K9
type: LocalParameter

131110
stoichiometry: 1.0
species: 130978
type: SpeciesReference

131626
value: 100.0
name: K2
type: LocalParameter

131494
stoichiometry: 1.0
species: 131038
type: SpeciesReference

COPASI5
is version of: GO:0016310
modifier: 131446
reactant: 131410
modifier: 131434
modifier: 075166
modifier: 075153
type: Reaction
modifier: 075178
name: 7
product: 131422
kinetic law: 131458
reversible: false
fast: false

131158
value: 15.0
name: K1
type: LocalParameter

131818
stoichiometry: 1.0
species: 131050
type: SpeciesReference

131830
stoichiometry: 1.0
species: 131038
type: SpeciesReference

131290
value: 0.1
name: k3
type: LocalParameter

131746
stoichiometry: 1.0
species: 130990
type: SpeciesReference

131278
value: 9.0
name: KI
type: LocalParameter

130942
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE
type: SBMLUnit

131026
is version of: P28482
constant: false
boundary condition: false
has only substance units: false
initial concentration: 999.999903688753
initial amount: NaN
in compartment: 130954
name: M
type: Species

COPASI4
type: Reaction
modifier: 075129
fast: false
kinetic law: 131362
modifier: 075117
modifier: 131350
modifier: 075141
reactant: 131302
is version of: GO:0016310
product: 131314
modifier: 131326
modifier: 131338
name: 4
reversible: false
modifier: 075105

130990
is version of: Q02750
constant: false
boundary condition: false
has only substance units: false
initial concentration: 3999.99961475501
initial amount: NaN
in compartment: 130954
name: MKK
type: Species

131710
value: 20.0
name: K5
type: LocalParameter

131170
value: 500.0
name: Ka
type: LocalParameter

130918
exponent: 1.0
scale: -3
multipler: 1.0
kind: LITRE
type: SBMLUnit

131482
value: 0.1
name: k7
type: LocalParameter

131578
stoichiometry: 1.0
species: 130978
type: SpeciesReference

130930
unit: 130942
name: substance
type: SBMLUnitsDef

131662
stoichiometry: 1.0
species: 131002
type: SpeciesReference

131470
value: 20.0
name: K7
type: LocalParameter

131806
value: 0.02
name: k6
type: LocalParameter

COPASI2
reactant: 131098
type: Reaction
reversible: false
name: 1
kinetic law: 131134
product: 131110
modifier: 131122
modifier: 075043
modifier: 075031
fast: false
is version of: GO:0016310

131998
value: 0.02
name: k10
type: LocalParameter

131146
value: 100.0
name: A
type: LocalParameter

131074
is version of: P51452
constant: false
boundary condition: false
has only substance units: false
initial concentration: 499.999951844377
initial amount: NaN
in compartment: 130954
name: P2
type: Species

131422
stoichiometry: 1.0
species: 131038
type: SpeciesReference

131086
is version of: P51452
constant: false
boundary condition: false
has only substance units: false
initial concentration: 499.999951844377
initial amount: NaN
in compartment: 130954
name: P3
type: Species

COPASI11
kinetic law: 131974
name: 10
modifier: 131962
modifier: 131950
product: 131926
fast: false
modifier: 075382
reactant: 131914
reversible: false
type: Reaction
modifier: 075370
is version of: GO:0016311
modifier: 075358
modifier: 131938

130906
unit: 130918
name: volume
type: SBMLUnitsDef

131722
value: 0.02
name: k5
type: LocalParameter

131314
stoichiometry: 1.0
species: 131014
type: SpeciesReference

131902
value: 0.02
name: k9
type: LocalParameter

131794
value: 20.0
name: K6
type: LocalParameter

130978
initial amount: NaN
has only substance units: false
is version of: P04049
boundary condition: false
type: Species
name: MKKK_P
initial concentration: 0.0
in compartment: 130954
constant: false
is version of: C00562

131386
value: 9.0
name: KI
type: LocalParameter

COPASI3
modifier: 075068
is version of: GO:0016310
reactant: 131194
type: Reaction
modifier: 131218
name: 3
modifier: 131242
reversible: false
modifier: 131230
product: 131206
modifier: 075093
modifier: 075080
modifier: 075055
fast: false
kinetic law: 131254

131014
initial concentration: 0.0
constant: false
boundary condition: false
initial amount: NaN
has only substance units: false
is version of: Q02750
in compartment: 130954
is version of: C00562
name: MKK_PP
type: Species

131926
stoichiometry: 1.0
species: 131026
type: SpeciesReference

131986
value: 20.0
name: K10
type: LocalParameter

131650
stoichiometry: 1.0
species: 131014
type: SpeciesReference

COPASI9
name: 6
type: Reaction
fast: false
reactant: 131734
product: 131746
modifier: 131770
reversible: false
modifier: 075286
modifier: 075310
modifier: 131758
kinetic law: 131782
is version of: GO:0016311
modifier: 075298

131566
value: 0.1
name: k8
type: LocalParameter

COPASI10
fast: false
name: 9
reactant: 131818
modifier: 075334
modifier: 075322
reversible: false
product: 131830
kinetic law: 131878
modifier: 131842
modifier: 131854
type: Reaction
is version of: GO:0016311
modifier: 075346
modifier: 131866

131062
is version of: P51452
constant: false
boundary condition: false
has only substance units: false
initial concentration: 99.9999903688752
initial amount: NaN
in compartment: 130954
name: P1
type: Species

131734
stoichiometry: 1.0
species: 131002
type: SpeciesReference

COPASI8
modifier: 075250
type: Reaction
product: 131662
modifier: 131686
name: 5
modifier: 075274
is version of: GO:0016311
reversible: false
fast: false
kinetic law: 131698
modifier: 131674
modifier: 075262
reactant: 131650

131590
stoichiometry: 1.0
species: 130966
type: SpeciesReference

131098
stoichiometry: 1.0
species: 130966
type: SpeciesReference

131410
stoichiometry: 1.0
species: 131026
type: SpeciesReference

131374
value: 20.0
name: K4
type: LocalParameter

130966
is version of: P04049
constant: false
boundary condition: false
has only substance units: false
initial concentration: 999.999903688753
initial amount: NaN
in compartment: 130954
name: MKKK
type: Species

131002
initial concentration: 0.0
has only substance units: false
is version of: Q02750
name: MKK_P
in compartment: 130954
is version of: C00562
type: Species
constant: false
boundary condition: false
initial amount: NaN

131638
value: 0.1
name: k2
type: LocalParameter

131302
stoichiometry: 1.0
species: 131002
type: SpeciesReference

131194
stoichiometry: 1.0
species: 130990
type: SpeciesReference

131554
value: 20.0
name: K8
type: LocalParameter

131914
stoichiometry: 1.0
species: 131038
type: SpeciesReference