%-------------------------------------------
% Text S7. Simulate and plot figure 9.
%-------------------------------------------

%-------------------------------------------
% plot_figure9.m
%-------------------------------------------
% author: Sohyoung Kim
% last updated: Jul-24-2009
% matlab 7.2.0.232 (R2006a) was used.
%% Description: this script generates figure 9-A
%               early DNA damage response
%               input: various levels of Mdm2 and MdmX production rate.
%               output: level of mRNA
%-------------------------------------------

%-------------------------------------------
% requirement to run this script.
%-------------------------------------------
% - need function definition file under current working directory: 
%       mdmx_p53_mdm2_model_full.m
%       model_check_osc_winit_full_function_varmdm2.m  
%           simulate with various levels of Mdm2 and return maximum values
%           of mRNA for first 180 min.
%-------------------------------------------

%-------------------------------------------
% set kinetic parameter values
% kinetic parameters used for figure 9 (see Table 1)
%-------------------------------------------
params_osc1=[    0.0033333
     0.003923
     0.015777
   0.00031555
     0.012239
  7.9939e-005
  7.5921e-005
     0.015777
   0.00031555
      0.18256
       30.559
      0.16082
      0.79167
      0.15833
  2.1726e-005
   0.00031553
     0.015777
   0.00031555
    0.0012239
       30.559
      0.16082
      0.79167
       342.74
      0.16082
      0.25964
      0.16082
      0.42063
      0.79177
       1.5429
      0.10161
      0.47149
       0.2555
      0.71695
    0.0062925
       2.7938
     0.065446
     0.055509
       3.7078];
       
oparams1=params_osc1;

% set initial condition.
x01=zeros(16,1);
x01(13)=1;

% set time period to simulate
rtime=180;

% simulate w/o MdmX
params_osc1(15)=0;
tp1s=logspace(-5, 1, 50);
e1_0=model_check_osc_winit_full_function_varmdm2(x01,params_osc1, 0.01, rtime, tp1s);

% simulate with various levels of MdmX 
params_osc1(15)=oparams1(15)/10;
e1_lowlow=model_check_osc_winit_full_function_varmdm2(x01,params_osc1, 0.01, rtime, tp1s);
params_osc1(15)=oparams1(15);
e1_same=model_check_osc_winit_full_function_varmdm2(x01,params_osc1, 0.01, rtime, tp1s);
params_osc1(15)=oparams1(15)*10;
e1_high=model_check_osc_winit_full_function_varmdm2(x01,params_osc1, 0.01, rtime, tp1s);
params_osc1(15)=oparams1(15)*100;
e1_highhigh=model_check_osc_winit_full_function_varmdm2(x01,params_osc1, 0.01, rtime, tp1s);

% plot simulation results as a function of Mdm2 basal production rate.
gind=1:50;
figure;
semilogx(tp1s(gind), e1_0((gind),2), 'b-','LineWidth', 2, 'MarkerSize', 7)
hold;
semilogx(tp1s(gind), e1_lowlow((gind),2), 'r.-','LineWidth', 2, 'MarkerSize', 7)
semilogx(tp1s(gind), e1_same((gind),2), 'gv-','LineWidth', 2, 'MarkerSize', 7)
semilogx(tp1s(gind), e1_high((gind),2), 'k+-','LineWidth', 2, 'MarkerSize', 7)
semilogx(tp1s(gind), e1_highhigh((gind),2), 'mo-','LineWidth', 2, 'MarkerSize', 7)

set(gca, 'FontSize', 12, 'FontWeight', 'bold');
xlabel('Basal production rate constant of Mdm2 (k15)')
ylabel('mRNA (species 15) [AU]');
legend('No MdmX', '1/10 fold', '1 fold', '10 fold', '100 fold');
legend('boxoff')