Table 1. The finalized TRAIL model reactions and parameters. Note that to simulate each KD condition, we imposed null parameter value(s) for all reaction(s) involving the KD molecule.

Reaction/process				k (1/s)	Remarks
1	Apo2/TRAIL	→	TRAIL receptor	8.13E-3	Binding of TRAIL ligand to receptor
2	TRAIL receptor	→	Receptor process 1	8.17E-3	O-glycosylation, internalization of receptors, formation of lipid rafts, etc.
3	Receptor process 1	→	Receptor process 2	7.89E-3
4	Receptor process 1	→	Y	1.04E-3	Activation of novel molecule Y
5	Y	→	MKK3/6	4.31E-1	Rapid activation of MKK3/6 via Y
6	Receptor process 2	→	FADD	1.08E-3	FADD binds to TRAIL receptors
7	FADD	→	pro-caspase-8	1.06E-3	pro-caspase-8 binds to FADD
8	pro-caspase-8	→	CUL3	1,99E-3	Activation of CUL3
9	pro-caspase-8	→	c-FLIP	1.00E-3*	Activation of cFLIP (*arbitrary value)
10	CUL3	→	Ubiquitination of caspase-8	1.00E-2	Ubiquitination of caspase-8
11	Ubiquitination of caspase-8	→	p62	9.92E-1	Activation of p62/sequestosome
12	Ubiquitination of caspase-8	→	TRAF2	8.67E-2	Activation of TRAF2 by pro-caspase-8
13	p62	→	Z	3.09E-1	Activation of novel molecule Z by p62
14	p62	→	RIP1	6.77E-2	Activation of RIP1 by p62
15	p62	→	caspase-8 (active form)	2.72E-2	Activation of caspase-8 (cleaved)
16	caspase-8 (active form)	→	tBid	1.13E-5	Activation of tBid by caspase-8
17	caspase-8 (active form)	→	caspase-3	1.48E-6	Activation of caspase-3 (extrinsic pathway)
18	tBid	→	mitochondria	5.09E-2	Apoptotic intrinsic pathway via tBid
19	mitochondria	→	Cytochrome C	2.64E-1	Activation of Cytochrome C
20	mitochondria	→	Smac	2.79E-1	Activation of Smac
21	Cytochrome C	→	caspase-3	2.81E-1	Activation of caspase-3 via apoptosome
22	Smac	→	caspase-3	1.68E-1	Smac-dependent activation of caspase-3
23	caspase-3	→	Apoptosis process	8.85E-3	caspase-3 depletion term
24	RIP1	→	IKK	4.00E-4	Activation of IKK by RIP1
25	RIP1	→	MKK3/6	5.04E-1	Activation of MKK3/6 by RIP1 (novel)
26	IKK	→	IκB	3.45E-1	Activation of IκB by IKK
27	IκB	→	NF-κB	8.99E-4	Activation of NF-κB by IκB
28	NF-κB	→	Survival process	1.00E-1*	NF-κB depletion term (*arbitrary value)
29	TRAF2	→	MKK3/6	7.24E-5	Activation of MKK3/6 by TRAF2
30	TRAF2	→	MKK4/7	2.63E-6	Activation of JNK pathway by TRAF2
31	MKK3/6	→	p38	2.37E-4	Activation of p38 by MKK3/6
32	p38	→	Survival process	1.31E-5	p38 depletion term
33	Y	→	Z	3.07E-1	Intermediates for delayed JNK activation
34	Z	→	X1	8.76E-4
35	X1	→	X2	3.18E-3
36	X2	→	X3	7.48E-3
37	X3	→	MKK4/7	2.21E-3	Activation of JNK through bypass
38	MKK4/7	→	JNK	1.81E-4	Activation of JNK by MKK4/7
39	JNK	→	Survival process	2.36E-4	JNK depletion term

Highlighted rows indicate novel features of the TRAIL signaling pathway.