All over or overall - Do we understand allostery?

Allostery is probably the most important concept in the regulation of cellular processes. Models to explain allostery are plenty. Each sheds light on different aspects but their entirety conveys an ambiguous feeling of comprehension and disappointment. Here, I discuss the most popular allostery models, their roots, similarities, and limitations. All of them are thermodynamic models. Naturally this bears a certain degree of redundancy, which forms the center of this review. After sixty years, many questions remain unanswered, mainly because our human longing for causality as base for understanding is not satisfied by thermodynamics alone. A description of allostery in terms of pathways, i.e., as a temporal chain of events, has been-, and still is-, a missing piece of the puzzle.