Limits...
Safe uses of Hill's model: an exact comparison with the Adair-Klotz model.

Konkoli Z - Theor Biol Med Model (2011)

Bottom Line: There are very few studies investigating the situations in which the model can be safely used.A strongly cooperative Adair-Klotz model can be replaced by a suitable Hill model in such a way that any property computed from the two models, even the one describing stochastic features, is approximately the same.The quantitative analysis showed that boundaries of the regions in the parameter space where the models behave in the same way exhibit a rather rich structure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chalmers University of Technology, Department of Microtechnology and Nanoscience, Bionano Systems Laboratory, Sweden. zorank@chalmers.se

ABSTRACT

Background: The Hill function and the related Hill model are used frequently to study processes in the living cell. There are very few studies investigating the situations in which the model can be safely used. For example, it has been shown, at the mean field level, that the dose response curve obtained from a Hill model agrees well with the dose response curves obtained from a more complicated Adair-Klotz model, provided that the parameters of the Adair-Klotz model describe strongly cooperative binding. However, it has not been established whether such findings can be extended to other properties and non-mean field (stochastic) versions of the same, or other, models.

Results: In this work a rather generic quantitative framework for approaching such a problem is suggested. The main idea is to focus on comparing the particle number distribution functions for Hill's and Adair-Klotz's models instead of investigating a particular property (e.g. the dose response curve). The approach is valid for any model that can be mathematically related to the Hill model. The Adair-Klotz model is used to illustrate the technique. One main and two auxiliary similarity measures were introduced to compare the distributions in a quantitative way. Both time dependent and the equilibrium properties of the similarity measures were studied.

Conclusions: A strongly cooperative Adair-Klotz model can be replaced by a suitable Hill model in such a way that any property computed from the two models, even the one describing stochastic features, is approximately the same. The quantitative analysis showed that boundaries of the regions in the parameter space where the models behave in the same way exhibit a rather rich structure.

Show MeSH
Similarity measures (weakly cooperative Adair-Klotz model, h = 3). Generated in the same way as Figure 1, but with a higher value for the Hill coefficient (h = 3). The parameters of the Hill model were optimized in the same way as for Figure 1, resulting in α = 0.5s-1, β = 0.083s-1. Increase in the Hill coefficient makes the discrepancy larger since there are more intermediate states that can be populated. The similarity in the distributions shape increases for large times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3104946&req=5

Figure 2: Similarity measures (weakly cooperative Adair-Klotz model, h = 3). Generated in the same way as Figure 1, but with a higher value for the Hill coefficient (h = 3). The parameters of the Hill model were optimized in the same way as for Figure 1, resulting in α = 0.5s-1, β = 0.083s-1. Increase in the Hill coefficient makes the discrepancy larger since there are more intermediate states that can be populated. The similarity in the distributions shape increases for large times.

Mentions: To which extent are the findings discussed so far sensitive to the value of the Hill coefficient? Figure 2 was constructed in the same way as Figure 1, but with a higher value of the Hill coefficient. To make the computations faster, the lowest possible value for the Hill coefficient was used, i.e. h = 3. In comparison to the h = 2 case, the fundamental similarity measure decreases further. It can be seen that increases, which indicates that the complement space becomes more populated. It is very likely that this is because more intermediate states are available. The shape similarity measure decreases for intermediate times, as the dotted curve has a deeper minimum than the dotted curve in Figure 1.


Safe uses of Hill's model: an exact comparison with the Adair-Klotz model.

Konkoli Z - Theor Biol Med Model (2011)

Similarity measures (weakly cooperative Adair-Klotz model, h = 3). Generated in the same way as Figure 1, but with a higher value for the Hill coefficient (h = 3). The parameters of the Hill model were optimized in the same way as for Figure 1, resulting in α = 0.5s-1, β = 0.083s-1. Increase in the Hill coefficient makes the discrepancy larger since there are more intermediate states that can be populated. The similarity in the distributions shape increases for large times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104946&req=5

Figure 2: Similarity measures (weakly cooperative Adair-Klotz model, h = 3). Generated in the same way as Figure 1, but with a higher value for the Hill coefficient (h = 3). The parameters of the Hill model were optimized in the same way as for Figure 1, resulting in α = 0.5s-1, β = 0.083s-1. Increase in the Hill coefficient makes the discrepancy larger since there are more intermediate states that can be populated. The similarity in the distributions shape increases for large times.
Mentions: To which extent are the findings discussed so far sensitive to the value of the Hill coefficient? Figure 2 was constructed in the same way as Figure 1, but with a higher value of the Hill coefficient. To make the computations faster, the lowest possible value for the Hill coefficient was used, i.e. h = 3. In comparison to the h = 2 case, the fundamental similarity measure decreases further. It can be seen that increases, which indicates that the complement space becomes more populated. It is very likely that this is because more intermediate states are available. The shape similarity measure decreases for intermediate times, as the dotted curve has a deeper minimum than the dotted curve in Figure 1.

Bottom Line: There are very few studies investigating the situations in which the model can be safely used.A strongly cooperative Adair-Klotz model can be replaced by a suitable Hill model in such a way that any property computed from the two models, even the one describing stochastic features, is approximately the same.The quantitative analysis showed that boundaries of the regions in the parameter space where the models behave in the same way exhibit a rather rich structure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chalmers University of Technology, Department of Microtechnology and Nanoscience, Bionano Systems Laboratory, Sweden. zorank@chalmers.se

ABSTRACT

Background: The Hill function and the related Hill model are used frequently to study processes in the living cell. There are very few studies investigating the situations in which the model can be safely used. For example, it has been shown, at the mean field level, that the dose response curve obtained from a Hill model agrees well with the dose response curves obtained from a more complicated Adair-Klotz model, provided that the parameters of the Adair-Klotz model describe strongly cooperative binding. However, it has not been established whether such findings can be extended to other properties and non-mean field (stochastic) versions of the same, or other, models.

Results: In this work a rather generic quantitative framework for approaching such a problem is suggested. The main idea is to focus on comparing the particle number distribution functions for Hill's and Adair-Klotz's models instead of investigating a particular property (e.g. the dose response curve). The approach is valid for any model that can be mathematically related to the Hill model. The Adair-Klotz model is used to illustrate the technique. One main and two auxiliary similarity measures were introduced to compare the distributions in a quantitative way. Both time dependent and the equilibrium properties of the similarity measures were studied.

Conclusions: A strongly cooperative Adair-Klotz model can be replaced by a suitable Hill model in such a way that any property computed from the two models, even the one describing stochastic features, is approximately the same. The quantitative analysis showed that boundaries of the regions in the parameter space where the models behave in the same way exhibit a rather rich structure.

Show MeSH