Jenkinson2011_EGF_MAPK

This is a model described in the article:
Thermodynamically Consistent Model Calibration in Chemical Kinetics.
Garrett Jenkinson and John Goutsias, BMC Systems Biology 2011 May 6;5(1):64.; PMID:21548948.
ABSTRACT:
BACKGROUND:
The dynamics of biochemical reaction systems are constrained by the fundamental laws of thermodynamics, which impose well-defined relationships among the reaction rate constants characterizing these systems. Constructing biochemical reaction systems from experimental observations often leads to parameter values that do not satisfy the necessary thermodynamic constraints. This can result in models that are not physically realizable and may lead to inaccurate, or even erroneous, descriptions of cellular function.
RESULTS:
We introduce a thermodynamically consistent model calibration (TCMC) method that can be effectively used to provide thermodynamically feasible values for the parameters of an open biochemical reaction system. The proposed method formulates the model calibration problem as a constrained optimization problem that takes thermodynamic constraints (and, if desired, additional non-thermodynamic constraints) into account. By calculating thermodynamically feasible values for the kinetic parameters of a well-known model of the EGF/ERK signaling cascade, we demonstrate the qualitative and quantitative significance of imposing thermodynamic constraints on these parameters and the effectiveness of our method for accomplishing this important task. MATLAB software, using the Systems Biology Toolbox 2.1, can be accessed from www.cis.jhu.edu/~goutsias/CSS lab/software.html. An SBML file containing the thermodynamically feasible EGF/ERK signaling cascade model can be found in the BioModels database.
CONCLUSIONS:
TCMC is a simple and flexible method for obtaining physically plausible values for the kinetic parameters of open biochemical reaction systems. It can be effectively used to recalculate a thermodynamically consistent set of parameter values for existing thermodynamically infeasible biochemical reaction models of cellular function as well as to estimate thermodynamically feasible values for the parameters of new models. Furthermore, TCMC can provide dimensionality reduction, better estimation performance, and lower computational complexity, and can help to alleviate the problem of data overfitting.
This model is a thermodynamically feasible version of a previous model
in the BioModels database,BIOMD0000000019, described in Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Schoeberl et al (2002), PMID:11923843.
The only difference between the present model and the model listed under BIOMD0000000019 are the values of the parameters.
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
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Thermodynamically consistent model calibration in chemical kinetics.
- Jenkinson G, Goutsias J
- BMC systems biology , 0/ 2011 , Volume 5 , pages: 64 , PubMed ID: 21548948
- Whitaker Biomedical Engineering Institute, The Johns Hopkins University, Baltimore, MD 21218, USA. goutsias@jhu.edu
- BACKGROUND: The dynamics of biochemical reaction systems are constrained by the fundamental laws of thermodynamics, which impose well-defined relationships among the reaction rate constants characterizing these systems. Constructing biochemical reaction systems from experimental observations often leads to parameter values that do not satisfy the necessary thermodynamic constraints. This can result in models that are not physically realizable and may lead to inaccurate, or even erroneous, descriptions of cellular function. RESULTS: We introduce a thermodynamically consistent model calibration (TCMC) method that can be effectively used to provide thermodynamically feasible values for the parameters of an open biochemical reaction system. The proposed method formulates the model calibration problem as a constrained optimization problem that takes thermodynamic constraints (and, if desired, additional non-thermodynamic constraints) into account. By calculating thermodynamically feasible values for the kinetic parameters of a well-known model of the EGF/ERK signaling cascade, we demonstrate the qualitative and quantitative significance of imposing thermodynamic constraints on these parameters and the effectiveness of our method for accomplishing this important task. MATLAB software, using the Systems Biology Toolbox 2.1, can be accessed from http://www.cis.jhu.edu/~goutsias/CSS lab/software.html. An SBML file containing the thermodynamically feasible EGF/ERK signaling cascade model can be found in the BioModels database. CONCLUSIONS: TCMC is a simple and flexible method for obtaining physically plausible values for the kinetic parameters of open biochemical reaction systems. It can be effectively used to recalculate a thermodynamically consistent set of parameter values for existing thermodynamically infeasible biochemical reaction models of cellular function as well as to estimate thermodynamically feasible values for the parameters of new models. Furthermore, TCMC can provide dimensionality reduction, better estimation performance, and lower computational complexity, and can help to alleviate the problem of data overfitting.
Submitter of this revision: Garrett Jenkinson
Modellers: Garrett Jenkinson
Metadata information
Connected external resources
Name | Description | Size | Actions |
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Model files |
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BIOMD0000000399_url.xml | SBML L2V1 representation of Jenkinson2011_EGF_MAPK | 247.06 KB | Preview | Download |
Additional files |
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BIOMD0000000399-biopax2.owl | Auto-generated BioPAX (Level 2) | 192.42 KB | Preview | Download |
BIOMD0000000399-biopax3.owl | Auto-generated BioPAX (Level 3) | 330.83 KB | Preview | Download |
BIOMD0000000399.m | Auto-generated Octave file | 37.73 KB | Preview | Download |
BIOMD0000000399.pdf | Auto-generated PDF file | 681.79 KB | Preview | Download |
BIOMD0000000399.png | Auto-generated Reaction graph (PNG) | 2.62 MB | Preview | Download |
BIOMD0000000399.sci | Auto-generated Scilab file | 185.00 Bytes | Preview | Download |
BIOMD0000000399.svg | Auto-generated Reaction graph (SVG) | 319.71 KB | Preview | Download |
BIOMD0000000399.vcml | Auto-generated VCML file | 897.00 Bytes | Preview | Download |
BIOMD0000000399.xpp | Auto-generated XPP file | 28.48 KB | Preview | Download |
BIOMD0000000399_urn.xml | Auto-generated SBML file with URNs | 239.34 KB | Preview | Download |
- Model originally submitted by : Garrett Jenkinson
- Submitted: May 6, 2011 8:16:29 PM
- Last Modified: Apr 8, 2016 6:21:34 PM
Revisions
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Version: 2
- Submitted on: Apr 8, 2016 6:21:34 PM
- Submitted by: Garrett Jenkinson
- With comment: Current version of Jenkinson2011_EGF_MAPK
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Version: 1
- Submitted on: May 6, 2011 8:16:29 PM
- Submitted by: Garrett Jenkinson
- With comment: Original import of BIOMD0000000399.xml.origin
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: Variable used inside SBML models
Species | Initial Concentration/Amount |
---|---|
x4 EGF:EGFR dimer [plasma membrane] ; Pro-epidermal growth factor ; Epidermal growth factor receptor |
0.0 item |
x9 AP-type membrane coat adaptor complex |
0.0 item |
x18 Growth factor receptor-bound protein 2 ; Ras GTPase-activating protein 1 ; Epidermal growth factor receptor ; Pro-epidermal growth factor |
0.0 item |
x30 Son of sevenless homolog 1 ; Growth factor receptor-bound protein 2 |
40000.0 item |
x39 Growth factor receptor-bound protein 2 ; SHC-transforming protein 2 |
0.0 item |
x40 SHC-transforming protein 2 |
0.0 item |
x41 RAF proto-oncogene serine/threonine-protein kinase |
40000.0 item |
x47 Dual specificity mitogen-activated protein kinase kinase 1 ; Mitogen-activated protein kinase kinase 1Mitogen-activated protein kinase kinase 1, isoform CRA acDNA FLJ76051, highly similar to Homo sapiens mitogen-activated protein kinase kinase 1 (MAP2K1), mRNA ; 176872 |
2.2E7 item |
Reactions | Rate | Parameters |
---|---|---|
x3 => x4 | k2*x3*x3-kr2*x4 | k2 = 4.80156E-4 peritempermin; kr2 = 0.5100538 permin |
x4 => x5 | k3*x4-kr3*x5 | k3 = 31.71871 permin; kr3 = 2.220991 permin |
x88 => x9 + x19 | k5*x88 | k5 = NaN permin |
x94 => x68 + x9 | k5*x94 | k5 = NaN permin |
x17 + x22 => x18 | k16*x17*x22-kr16*x18 | kr16 = 0.4509308 permin; k16 = 4.021305E-4 peritempermin |
x25 => x15 + x30 | k34*x25-kr34*x15*x30 | k34 = 0.2467995 permin; kr34 = 1.283286E-4 peritempermin |
x65 => x17 + x39 | k37*x65-kr37*x17*x39 | kr37 = 5.477036E-6 peritempermin; k37 = 29.34687 permin |
x40 => x31 | Vm36*x40/(Km36+x40) | Km36 = 7.719778E14 items; Vm36 = 615.0325 itemspermin |
x73 => x41 + x44 | k43*x73 | k43 = 51.60945 permin |
x47 + x45 => x48 | k44*x47*x45-kr44*x48 | kr44 = 0.5985189 permin; k44 = 0.001406622 peritempermin |
(added: 03 Nov 2011, 14:33:22, updated: 03 Nov 2011, 14:33:22)