Baltazar D' Aguda

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Modeling Activation of Caspases
Baltazar D. Aguda Mathematical Biosciences
Institute Ohio State University bdaguda_at_gmail.com
Talk presented to the Andrea Doseff Lab Ohio
State Univ 5 Feb2007
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PLAYMATES
not these
but this
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Download a COOL MODELING TOOL BerkeleyMadonna
http//www.berkeleymadonna.com
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MODELING CASPASE-MEDIATED APOPTOSIS
Figure from Zheng Flavell, 2000
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MODEL OF EISSING ET AL.
Eissing T, Conzelmann H, Gilles ED, Allgower F,
Bullinger E, Scheurich P. Bistability analyses
of a caspase activation model for
receptor-induced apoptosis. J Biol Chem. 2004
Aug 27279(35)36892-7.
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MODEL OF EISSING ET AL.
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CODING MODEL INTO BERKELEYMADONNA
Program initially expects you to type
in equations and parameter values but you can
open a pre-typed text file containing these
information.
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TEXT FILE FOR EISSING MODEL
METHOD STIFF STARTTIME 0 STOPTIME 200 DT
0.01 Eissing Model, Baltz / 3 Feb 2007
differential equations d/dt(C8)
vm9-(v9v2) d/dt(C8s) (v2vm11)-(v5v11) d/dt(C3
) vm10-(v1v10) d/dt(C3s) (v1vm3)-(v3v6) d/d
t(IAP) (vm3vm8)-(v3v8v4) d/dt(iC3sIAP)
v3-(vm3v7) d/dt(BAR) (vm11vm12)-(v11v12) d/dt
(iC8sBAR) v11-(vm11v13) rate
expressions v1 k1 C8sC3 v2 k2C3sC8 v3
k3C3sIAP vm3 km3iC3sIAP v4 k4C3sIAP v5
k5C8s v6 k6C3s v7 k7iC3sIAP v8
k8IAP vm8 km8 v9 k9C8 vm9 km9 v10
k10C3 vm10 km10 v11 k11C8sBAR vm11
km11iC8sBAR v12 k12BAR vm12 km12 v13
k13iC8sBAR
initial conditions init C8 0.01 init C8s
0.001 init C3 0.001 init C3s 0.0001 init IAP
0.01 init iC3sIAP 0.0 init BAR 0.01 init
iC8sBAR 0.0 parameter values k1 5.0 k2
1.0 k3 10.0 km3 0.05 k4 10.0 k5 0.005 k6
0.005 k7 0.003 k8 0.005 km8 0.001 k9
0.003 km9 0.005 k10 0.002 km10 0.005 k11
5.0 km11 0.05 k12 0.001 km12 0.00001 k13
0.05
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parameter sliders
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Eissing T, Conzelmann H, Gilles ED, Allgower F,
Bullinger E, Scheurich P. Bistability analyses
of a caspase activation model for
receptor-induced apoptosis. J Biol Chem. 2004
Aug 27279(35)36892-7.
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A SIMPLE MODEL INCLUDING PKCd
pkc-model-1
v1 k1C3aC8 v2 k2aC8aC3 k2bC3aC3
k2cPKCC3/(Kmc3C3) v3 k3 vm3
km3C3aPKC/(KmpkcPKC) km3bPKC v4 k4 vm4
km4C3aIAP km4bIAP v5 k5IAPC3a v6
k6C8a v7 k7 vm7 km7C8 v8 k8 vm8 km8C3
d/dt(C8) v7-(vm7v1) d/dt(C8a) v1-v6 d/dt(C3)
v8-(vm8v2) d/dt(C3a) v2-v5 d/dt(IAP)
v4-vm4 d/dt(PKC) v3-vm3
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RUN 1 (pkc-model-1)
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RUN 1 (pkc-model-1)
METHOD STIFF STARTTIME 0 STOPTIME 200 DT
0.01 Simple Model with PKC-delta, Baltz / 3
Feb 2007 differential equations d/dt(C8)
v7-(vm7v1) d/dt(C8a) v1-v6 d/dt(C3)
v8-(vm8v2) d/dt(C3a) v2-v5 d/dt(IAP)
v4-vm4 d/dt(PKC) v3-vm3 v1 k1C3aC8 v2
k2aC8aC3 k2bC3aC3 k2cPKCC3/(Kmc3C3) v3
k3 vm3 km3C3aPKC/(KmpkcPKC) km3bPKC v4
k4 vm4 km4C3aIAP km4bIAP v5
k5IAPC3a v6 k6C8a v7 k7 vm7 km7C8 v8
k8 vm8 km8C3
init C8 1.0 init C8a 0.001 init C3 1.0 init
C3a 0.0 init IAP 0.1 init PKC 0.05 k1
1.0 k2a 1.0 k2b 1.0 k2c 1.0 k3 0.4 km3
10 km3b 1.0 k4 0.5 km4 0.1 km4b 1.5 k5
0.5 k6 1.0 k7 0.5 km7 0.1 k8 0.01 km8
0.01 Kmc3 1.0 Kmpkc 1.0
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TO BE DEVELOPED model with details on Hsp27
PKCd