Computational Systems Biology
Sauro Lab
University of Washington
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Software Downloads:

1. SBW
2. JDesigner
3. Jarnac
4. WinSCAMP
5. Matlab Interface
6. Optimization
6. Bifurcation
 
maintained by Frank Bergmann
 
 
 
 

JSim/SBW Course

Schedule

  1. Installing software
  2. Simple models with the software
  3. Steady-State
  4. Linear Pathways
  5. Control of Pathways
  6. Negative Feedback
  7. Branch Points

Software

Please install SBW from: SetupSBW.exe

Slides

Introductory Slides

Compute the steady state for this model:

// Open Model
p = defn cell
     ext Xo, X1;

     Xo -> S1; k1*Xo - k2*S1;
     S1 -> S2; k3*S1 - k3*S2;
     S2 -> X1; k5*S2 - k6*X1;
end;

p.Xo = 4;
p.X1 = 0;
p.k1 = 1.2; p.k2 = 0.45;
p.k3 = 0.56; p.k4 = 0.2;
p.k5 = 0.89; p.k6 = 0;

What happens when we perturb a variable species?

// Perturbing a species at a specific time
p = defn cell
     ext Xo, X1;

     Xo -> S1; k1*Xo - k2*S1;
     S1 -> S2; k3*S1 - k3*S2;
     S2 -> X1; k5*S2 - k6*X1;

     at(gt(time,10)): S1 = S1*1.2;

end;

p.Xo = 4;
p.X1 = 0;
p.k1 = 1.2; p.k2 = 0.45;
p.k3 = 0.56; p.k4 = 0.2;
p.k5 = 0.89; p.k6 = 0;

What happens when we perturb enzyme levels?

// Perturbing enzymes
p = defn cell
     ext Xo, X1;

     Xo => S1; (Vmax1/Km1)*(Xo - S1/Keq1)/(1 + Xo/Km1 + S1/Km2);
     S1 => S2; (Vmax2/Km2)*(S1 - S2/Keq2)/(1 + S1/Km3 + S2/Km4);
     S2 -> X1; Vmax3*S2/(Km5 + S2);

end;

p.Xo = 4;
p.X1 = 0;
p.Vmax1 = 1.4; p.Vmax2 = 2.3; p.Vmax3 = 0.67;
p.Km1 = 0.5;  p.Km2 = 0.34;
p.Km3 = 0.78; p.Km4 = 1.2;
p.Km5 = 0.3;
p.Keq1 = 4.5; p.Keq2 = 2.3; p.Keq3 = 1.2;

Carry out the following experiments:

  1. Compute the steady state
  2. Record the Steady State Flux, J
  3. Increase Vmax1 by 5% and recompute the steady state, record JP
  4. Compute the ratio of the fractional change in J and Vmax1, that is

Compute

C1 = ((JP-J)/J) / 0.05

  1. Do this for each enzyme and compute C2, C3
  2. Compute the sum, C1 + C2 + C3
  3. What do you observe?

Steady State Properties

Properties of Linear Pathways

Branch Pathways

Simple Branch

Negative Feedback

// Feedback model
// Negative feedback in a metabolic pathway

p = defn feedback


J0: $X0 -> S1; VM1*(X0-S1/Keq1)/(1+X0+S1+S4^h);
J1: S1 -> S2;  VM2*(10*S1-2*S2)/(1+S1+S2);
J2: S2 -> S3;  VM3*(10*S2-2*S3)/(1+S2+S3);
J3: S3 -> S4;  VM4*(10*S3-2*S4)/(1+S3+S4);
J4: S4 -> $X1; VM5*S4/(KS4+S4);


end;

p.X0 = 10; p.X1 = 0;
p.S1 = 0;
p.S2 = 0;
p.S3 = 0;
p.S4 = 0;
p.VM1 = 10; p.VM2 = 5; p.VM3 = 4; p.VM4 = 2.5; p.VM5 = 2.5;
p.Keq1 = 10;
p.h = 2;
p.KS4 = 0.5;

Same model with strong negative feedback

p = defn feedback

var S1, S2, S3, S4;
ext X0, X1;

J0: $X0 -> S1; VM1*(X0-S1/Keq1)/(1+X0+S1+pow(S4,h));
J1: S1 -> S2; VM2*(10*S1-2*S2)/(1+S1+S2);
J2: S2 -> S3; VM3*(10*S2-2*S3)/(1+S2+S3);
J3: S3 -> S4; VM4*(10*S3-2*S4)/(1+S3+S4);
J4: S4 -> $X1; VM5*S4/(KS4+S4);

end;

p.X0 = 10; p.X1 = 0;
p.S1 = 0;
p.S2 = 0;
p.S3 = 0;
p.S4 = 0;
p.VM1 = 27.27001909;
p.Keq1 = 21.03001701;
p.h = 7.27001727;
p.VM2 = 0.39001026; p.VM3 = 0.54001045;
p.VM4 = 2.5;        p.VM5 = 2.43751325;
p.KS4 = 0.30151201;

 
tutorials/uwjsim2010.txt · Last modified: 2010/08/26 08:31 by fbergman
 

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