 %  DOQCS : http://doqcs.ncbs.res.in/ 
 %  Accession Name = MAPK_Asthagiri_enz_fb 
 %  Accession Number = 46 
 %  Transcriber = Pradeep Kumar S, NCBS 
 %  Developer = Anand R. Asthagiri and Douglas A. Lauffenburger 
 %  Species = Chinese hamster (Cricetulus griseus); mammalian 
 %  Tissue =  Ovary - CHO cell line 
 %  Cell Compartment =  Surface + cytosol 
 %  Notes =  This is a complex model to examine mechanisms that govern MAPK pathway dynamics in Chinese hamster ovary (CHO) cell lines, particularly the role of enzyme targeted negative feedback mechanism in generating downstream signal adaptation. This model simulates the results as per the simulation conditions specified for figure 7B of the paper by <a href =http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11312698>Asthagiri AR and Lauffenburger DA. Biotechnol Prog. (2001) 17(2):227-39</a>.<br> However, there is some discrepancy with the outputs shown in Figure 7B. 
 
   % Note: All the concentrations are in micro Mole (uM)

function moose_convert
%Matlab simulation for chemical kinetics

% Saved on Wed Feb  2 16:42:46 2005

% Automatically generated from kkit model in MOOSE by conv_matlab

global buff;
tspan=[0, 6000];
% Molecule names
molnames = {
'1 /kinetics/R'
'2 /kinetics/C'
'3 /kinetics/C*'
'4 /kinetics/C2'
'5 /kinetics/A1'
'6 /kinetics/A2'
'7 /kinetics/C*A1'
'8 /kinetics/A1A2'
'9 /kinetics/E0*'
'10 /kinetics/E0*/E1_activ/E1_activ_cplx'
'11 /kinetics/E1'
'12 /kinetics/E1*'
'13 /kinetics/E1*/E2_activ/E2_activ_cplx'
'14 /kinetics/P1'
'15 /kinetics/P1/E1*_deactiv/E1*_deactiv_cplx'
'16 /kinetics/E2'
'17 /kinetics/E2*'
'18 /kinetics/E2*/E3_activ/E3_activ_cplx'
'19 /kinetics/P2'
'20 /kinetics/P2/E2*_deactiv/E2*_deactiv_cplx'
'21 /kinetics/E3'
'22 /kinetics/E3*'
'23 /kinetics/E3*/E4_activ/E4_activ_cplx'
'24 /kinetics/P3'
'25 /kinetics/P3/E3*_deactiv/E3*_deactiv_cplx'
'26 /kinetics/E4'
'27 /kinetics/E4*'
'28 /kinetics/E4*/E5_activ/E5_activ_cplx'
'29 /kinetics/E4*/E4*_enz_targeted_fb/E4*_enz_targeted_fb_cplx'
'30 /kinetics/P4'
'31 /kinetics/P4/E4*_deactiv/E4*_deactiv_cplx'
'32 /kinetics/E5'
'33 /kinetics/P5'
'34 /kinetics/P5/E5*_deactiv/E5*_deactiv_cplx'
'35 /kinetics/E5*'
'36 /kinetics/E2-'
};

bufnames = {
'1 /kinetics/L'
};

sumtotnames = {
};

% Initial concs of 36 molecules
y0(1) = 0.42735;
y0(2) = 0;
y0(3) = 0;
y0(4) = 0;
y0(5) = 0.042735;
y0(6) = 0.042735;
y0(7) = 0;
y0(8) = 0;
y0(9) = 0;
y0(10) = 0;
y0(11) = 0.042735;
y0(12) = 0;
y0(13) = 0;
y0(14) = 0.0213675;
y0(15) = 0;
y0(16) = 0.042735;
y0(17) = 0;
y0(18) = 0;
y0(19) = 0.0213675;
y0(20) = 0;
y0(21) = 0.042735;
y0(22) = 0;
y0(23) = 0;
y0(24) = 0.0213675;
y0(25) = 0;
y0(26) = 0.042735;
y0(27) = 0;
y0(28) = 0;
y0(29) = 0;
y0(30) = 0.0213675;
y0(31) = 0;
y0(32) = 0.042735;
y0(33) = 0.0213675;
y0(34) = 0;
y0(35) = 0;
y0(36) = 0;
buff(1) = 0.03;
% Call the ODE solver and display results
[t, y] = ode23s(@f, tspan, y0);

hold on;
plot(t,y(:,12));
plot(t,y(:,17));
plot(t,y(:,22));
plot(t,y(:,27));
plot(t,y(:,35));
plot(t,y(:,9));
% Evaluation function
function dydt = f(t, y)
global buff;
dydt = [
 - 0.166601 * buff(1) * y(1) + 0.005 * y(2)
 + 0.166601 * buff(1) * y(1) - 0.005 * y(2) - 2 * y(2)*y(2) + 2 * y(4)
 + 0.833 * y(4) - 0.0833 * y(3) - 5.00011 * y(3) * y(5) + 0.50001 * y(7) - 5.00011 * y(8) * y(3) + 0.50001 * y(9)
 + 0.999999 * y(2)*y(2) - 1 * y(4) - 0.833 * y(4) + 0.0833 * y(3)
 - 5.00011 * y(3) * y(5) + 0.50001 * y(7) - 5.00011 * y(6) * y(5) + 0.50001 * y(8)
 - 5.00011 * y(7) * y(6) + 0.50001 * y(9) - 5.00011 * y(6) * y(5) + 0.50001 * y(8)
 + 5.00011 * y(3) * y(5) - 0.50001 * y(7) - 5.00011 * y(7) * y(6) + 0.50001 * y(9)
 + 5.00011 * y(6) * y(5) - 0.50001 * y(8) - 5.00011 * y(8) * y(3) + 0.50001 * y(9)
 + 5.00011 * y(7) * y(6) - 0.50001 * y(9) + 5.00011 * y(8) * y(3) - 0.50001 * y(9) - 9.99999 * y(11) * y(9) + 0.5 * y(10) + 0.1 * y(10)
 + 9.99999 * y(11) * y(9) - 0.5 * y(10) - 0.1 * y(10)
 - 9.99999 * y(11) * y(9) + 0.5 * y(10) + 0.1 * y(15)
 + 0.1 * y(10) - 9.99999 * y(12) * y(14) + 0.5 * y(15) - 9.99999 * y(16) * y(12) + 0.5 * y(13) + 0.1 * y(13)
 + 9.99999 * y(16) * y(12) - 0.5 * y(13) - 0.1 * y(13)
 - 9.99999 * y(12) * y(14) + 0.5 * y(15) + 0.1 * y(15)
 + 9.99999 * y(12) * y(14) - 0.5 * y(15) - 0.1 * y(15)
 - 9.99999 * y(16) * y(12) + 0.5 * y(13) + 0.1 * y(20)
 + 0.1 * y(13) - 9.99999 * y(17) * y(19) + 0.5 * y(20) - 9.99999 * y(21) * y(17) + 0.5 * y(18) + 0.1 * y(18) - 9.99999 * y(17) * y(27) + 0.5 * y(29)
 + 9.99999 * y(21) * y(17) - 0.5 * y(18) - 0.1 * y(18)
 - 9.99999 * y(17) * y(19) + 0.5 * y(20) + 0.1 * y(20)
 + 9.99999 * y(17) * y(19) - 0.5 * y(20) - 0.1 * y(20)
 - 9.99999 * y(21) * y(17) + 0.5 * y(18) + 0.1 * y(25)
 + 0.1 * y(18) - 9.99999 * y(22) * y(24) + 0.5 * y(25) - 9.99999 * y(26) * y(22) + 0.5 * y(23) + 0.1 * y(23)
 + 9.99999 * y(26) * y(22) - 0.5 * y(23) - 0.1 * y(23)
 - 9.99999 * y(22) * y(24) + 0.5 * y(25) + 0.1 * y(25)
 + 9.99999 * y(22) * y(24) - 0.5 * y(25) - 0.1 * y(25)
 - 9.99999 * y(26) * y(22) + 0.5 * y(23) + 0.1 * y(31)
 + 0.1 * y(23) - 9.99999 * y(27) * y(30) + 0.5 * y(31) - 9.99999 * y(32) * y(27) + 0.5 * y(28) + 0.1 * y(28) - 9.99999 * y(17) * y(27) + 0.5 * y(29) + 0.1 * y(29)
 + 9.99999 * y(32) * y(27) - 0.5 * y(28) - 0.1 * y(28)
 + 9.99999 * y(17) * y(27) - 0.5 * y(29) - 0.1 * y(29)
 - 9.99999 * y(27) * y(30) + 0.5 * y(31) + 0.1 * y(31)
 + 9.99999 * y(27) * y(30) - 0.5 * y(31) - 0.1 * y(31)
 - 9.99999 * y(32) * y(27) + 0.5 * y(28) + 0.1 * y(34)
 - 9.99999 * y(35) * y(33) + 0.5 * y(34) + 0.1 * y(34)
 + 9.99999 * y(35) * y(33) - 0.5 * y(34) - 0.1 * y(34)
 + 0.1 * y(28) - 9.99999 * y(35) * y(33) + 0.5 * y(34)
 + 0.1 * y(29)
];

% end of model
