On the Emergence of Single Versus Multi-State Allostery

Several physical mechanisms have been proposed to explain allostery in proteins. They differ by the number of internal states that they assume a protein occupy, leaving open question what controls emergence these distinct forms allostery. Here, we analyze simplified model under range and evolutionary constraints. We find two archetypal can emerge through evolution: single-state mechanism where ligand binding induces displacement along soft normal mode or multi-state switch across an energy barrier different stable state. Importantly, whenever are possible, confers stronger allosteric effect thus selective advantage. This work defines essential constraints on single allostery, sets stage for theory its origins.