Binding of R2 to A

The ScbR homo-dimer (R₂) forms a complex with ScbA (A).

Chemical equation

$A + R_{2} \rightleftharpoons A-R_{2}$

Rate equation

$r= \frac{k^{-}_{3}}{K_{d3}}\cdot [A]\cdot [R_{2}] - k^{-}_{3}\cdot [A-R_{2}]$

Parameters

The parameters of this reaction are the dissociation constant for binding of ScbR to ScbA ($K_{d3}$) and the dissociation rate for binding of ScbR to ScbA ($k^{-}_{3}$). Since there is no concrete evidence of the existence of the ScbA-ScbR complex so far, it is possible that the interaction between the two proteins is unstable/ transient and therefore the parameter values reflect this belief. The values of such complexes according to the literature , lie in the millimolar or micromolar scale.

• 

  Ozbabacan et al. 2011
• 

  Perkins et al. 2010

Name	Value	Units	Value in previous GBL model	Remarks-Reference
$K_{d3}$	$10^{3}-10^{6}$	$nM$	$0.083 nM^{-1} s^{-1}$ (Range tested: $10^{-7}-10^{-1} nM^{-1} s^{-1}$) (Bistability range: $0.083-0.12 nM^{-1} s^{-1}$)	According to the Ozbabacan et al. association constants for transient protein protein interactions lie in the millimolar or micromolar range. Ozbabacan et al. 2011
$k^{-}_{3}$	$60-6 \cdot 10^{4}$	$min^{-1}$	$630 s^{-1}$ (Range tested: $0-10^{3} s^{-1}$) (Bistability range: $460-630 s^{-1}$)	According to Northrup et al. the $K_{a}$ of protein-protein bond formations occur in the order of $10^{6} M^{-1}s^{-1}$. Therefore, this value is used to calculate the dissociation rate for the ScbR-ScbA binding. Therefore the range of the $k^{-}_{3}$ values is calculated as per $k^{-}_{3}=K_{d3} \cdot K_{a}$. Northrup et al. 1992

Parameters with uncertainty

Since the values we are using for this parameter correspond to generic association constant values of a wide range of protein-protein interactions and not specifically to GBL or related systems, we wish to explore the whole range of values and investigate the conditions under which the ScbR-ScbA complex formation would be feasible. Therefore, we set the mode of the log-normal distribution for $K_{d3}$ to $7 \cdot 10^{4} nM$ and the confidence interval factor to $10$. Thus, the range where 95% of the values are found is between $7 \cdot 10^{3} nM$ and $7 \cdot 10^{5} nM$.

Similarly, since the two parameters are interconnected, the mode of the log-normal distribution for $k^{-}_{3}$ is set to $2 \cdot 10^{4} min^{-1}$ and the confidence interval factor to $2.5$. This means that the range where 95% of the values are found is between $8 \cdot 10^{3} nM$ and $5 \cdot 10^{4}$ $min^{-1}$.

The probability distributions for the two parameters, adjusted accordingly in order to reflect the above values, are the following:

500px 500px

The location and scale parameters of the distributions are:

Parameter	μ	σ
$K_{d3}$	$11.9714$	$0.90284$
$k^{-}_{3}$	$10.0888$	$0.4305$