About this model
====================

This is a bond-graph model of the metabolism of generic receptor tyrosine kinase (RTK) in the mammalian cell.

    **INPUTS:** 
        - Ligand (L) stimulus  
        
    **OUTPUTS:** 
        - Change in molar amount of phosphorylated RTK K\ :sub:`2`\ P\ :sub:`n`\ 
        
    **REACTIONS:** 
		- Re\ :sub:`1`\ : the binding of L to one RTK (K\ :sub:`1`)
		- Re\ :sub:`2`\ : formation of complex of two RTK molecules which have dimerized, with ligand present (LK\ :sub:`1` K\ :sub:`2`).
		- Re\ :sub:`3`\ : autophosphorylation of RTKs in the dimer.         
		- Re\ :sub:`4`\ : binding of ubiquitin to resulting ligand-RTK complex
		- Re\ :sub:`5`\ : Ubiquitin-tagged complex gets sorted for RTK to be recycled, and other constituents to be degraded.
		- Re\ :sub:`6`\ : Ubiquitin-tagged complex gets sorted for RTK to be degraded by hydrolysis inside a lysosome.
		

Model status
=============

The current CellML implementation runs in OpenCOR.


Model overview
===================

The following model of RTK action is based on what is widely known in literature. 


.. figure:: exposure/BG_diagram.png
   :width: 100%
   :align: center
   :alt: BG RTK reaction
   
   Bond-graph formulation of the generic RTK network. Because this model is generic, :math:`{n}` would change depending on the chosen reaction. 'E' represents the RTK protein; 'tag' represents the protein that has been sorted for either recycling (reaction 5) or degradation (reaction 6) by ubiquitin U.

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.. csv-table:: List of chemical species
   :header: "Abbreviation", "Name"
   :widths: 5, 15 
   
   "K", "Receptor tyrosine kinase (RTK)"
   "L", "Ligand"
   "P\ :sub:`i`", "Phosphate"
   "U", "Ubiquitin"
   
Parameter finding
~~~~~~~~~~~~~~~~~
A description of the process to find bond-graph parameters is shown in the folder `parameter_finder <parameter_finder>`_, which relies on the:

1. stoichiometry of system

2. kinetic constants for forward/reverse reactions

  - If not already, all reactions are made reversible by assigning a small value to the reverse  direction.
  
3. `linear algebra script <https://models.physiomeproject.org/workspace/b2d/file/722d3150e09052999ed676cd31c39aa16e20a0bd/parameter_finder/kinetic_parameters_RTK.py>`_. 

Here, this solve process is performed in Python.