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I am highly suspect of the ability of MD simulations to accurately predict binding rates from the different structural models.
We also collected the mean binding rates from the simulations we did in Fig. 12 B, in which ions were removed from the solution after they were bound.
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Despite this, the corresponding constant binding rate from the continuous model can reproduce the binding events registered in the RW model.
In Fig. 12 C, the red lines represent 95% confidence intervals of the true mean binding rate from the 100 runs.
To distinguish the most dominant kinetic parameter values in determining GCN4 ribosome loading, we took the relative ternary complex binding rates from Model 2. Using MATLAB, we placed these rates in a stochastic simulation framework that describes the behaviour of ribosomes on the GCN4 mRNA.
Note that, the expression for the binding rate from our model is exactly the same as that derived by chemical kinetic modeling of reaction rates.
Instead we registered the mean binding rate from each run and compared this with the rate predicted from the continuous model.
Binding rate can vary depending on transfection frequency, so we compared the binding rates between cells from the same transfection but with one set of cells induced to express Fj.
Here, we see that the binding rates follow the number of registered binding events from Fig. 12 B, and not the predicted rate from the continuous model.
Also shown in Fig. 2c and f are the voxel-scale binding rates determined from Eqs. (17) and (19).
For example, based on the basic network N1 in Figure 1, the differential equations for the change of concentration of AKT and p53 were derived as: d d t A K T = - A K T ⋅ r c 18 + H E R 2 ⋅ r c 20, d d t p 53 = - p 53 ⋅ r c 10 + A K T ⋅ | r c 18 - p 53 ⋅ r c 27, where rc18 is the binding rate constant from AKT to p53 and [AKT] is the concentration of the AKT molecule.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com