CHBI308 – Spring 2021

Reaction Engineering
CellDesigner Project
Please DO NOT forget to write down names and student IDs of each group member.

Cell Designer Project

The EGFR pathway regulates cell growth, survival, proliferation and communicates a signal (EGF) from
a receptor (EGFR) on the surface of the cell to the DNA in the nucleus of the cell. Proteins including EGFR
in this pathway are activated by phosphorylation (addition of phosphoryl groups), which acts as an “on” or
“off” switch.

a) Discuss cellular functions of EGFR pathway (provide references) and illustrate the part of the
pathway given below (by hand). (20)
b) Considering only the 3 reversible and 1 irreversible reactions given below, model the pathway
with differential equations using CellDesigner. Plot and discuss the concentration profile of the
species. Comment on dependency of the concentration of each species. (40)
c) Create a table with species’ names, time points with their highest concentration and the highest
concentration values (15)
d) Change kf1 to 0.X1Y1 and [EGFR]0 = 10*X2Y2 where X1Y1 is the last two digits of one of your ID
number and X2Y2 is the last two digits of one of the other group member’s ID number. Discuss
how these changes affect the concentration profiles. (25)

Provide screenshots of the model, species tab, reactions tab, parameters tab and graphs.

1. EGF + EGFR EGF-EGFR

2. EGF-EGFR+ EGF-EGFR 2 EGF-EGFR

3. 2 EGF-EGFR 2 EGF-EGFR** (while being transported from ECM to Cellular

Cytoplasm)

4. 2 EGF-EGFR + SHC àSHC*

* : phosphorylated, active [EGFR] proteins

** : double phosphorylated active [EGFR] proteins (No specific GTP bound is necessary)

2 EGF-EGFR: EGF-EGFR dimer (EGFR is activated after dimerization)

Rate parameters:
kf1 = 0.00237 kr1 = 0.1146248 Initial Amounts:
kf2 = 4.8E-4 kr2 = 0.51 [EGF]0 = 4962
kf3 = 0.5 kr3 = 2.8643 [SHC]0= 12000
kf4 = 5.1741 kr4 = 1.5 [EGFR]0 = 50000
 Assume zero concentration for all other proteins.

Hint: First, write the rate equations for each reaction using the example below. Then enter these reactions
together with the rate constants and initial concentrations into the CellDesigner.

EGF + EGFR EGF-EGFR

-r1 = kf1*[EGF][EGFR] – kr1*[ EGF-EGFR]

Good luck

(For any questions contact us: igoktan14@ku.edu.tr )

P.S. : The parameters related to the first 3 reactions are obtained from the literature while the
parameters for the 4th reaction is randomly assigned.