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However, as such measurements are almost always performed in non-native environments, the central question is to which extent the ensemble of conformations existing in a given membrane-mimicking environment reflects those present in membranes

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The review would benefit from a bit more text on how this notion impacts the balance between desired therapeutic effects, "diluted" effects from dimer-mediated versus non-dimer effects, and undesired off-target effects (which are discussed some in terms of receptor specificity, but not in terms of anatomy, where the same dimer may have different effects in different brain regions).” Response: We have added a new section title “General treatment approaches” before the concluding remarks