Is there a clear correlation/no correlation between having a strong binding to a receptor and having a functional activity (agonism/antagonism) on it? and Vice versa? particularly for GPCR. In other words:
1. What if we have a strong binding in the low nM range on a particular GPCR and no functional activity?
2. or if we have a functional antagonistic effect on another GPCR we did not test binding on it yet! to what extent should the functional assay in this case indicate a "must to do" binding"
Correlation between binding and functional activity? - ResearchGate. Available from: https://www.researchgate.net/post/correlation_between_binding_and_functional_activity#view=58d68baf96b7e42a1c707f78 [accessed Mar 25, 2017].
That's a question quite difficult to answer. I would say that in general there is some/little correlation, since a ligand strongly bound to protein will almost always alter its dynamic structure, hence have some effect on its activity. But the change of activity can be either way (agonists / antagonists) as well as there may be simply no change in particular activity, but e.g. change in a different one, if the protein has mutliple activities.
In GPCR it may be different, since due to the GPCR structure most or all strong binders will bind inside the GPCR, almost always altering at least the rigidness of helices and possibly also the rigidness of the loops. So I would say that in GPCRs most strong binding ligands will almost always have some effect on functional activity, but without functional assays it would be hard to tell what is the effect.
Thanks Dr. Bartosz for your answer, but
1. What if we have a strong binding in the low nM range on a particular GPCR and no functional activity?
2. or if we have a functional antagonistic effect on another GPCR we did not test binding on it yet! to what extent should the functional assay in this case indicate a "must to do" binding"
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