Methods for inferring allostery typically rely on observing concerted structural changes. A system with two distant sites may jump between alternative configurations in some coupled fashion. That is, the structure of site A may be coupled to the configuration of site B, and vice versa. This extreme ex-ample of conformational selection could be inferred by comparing structures of proteins before and after some perturbation to one of the sites is introduced (such as ligand binding). Indeed, crystallography and HDX methods have proved useful in revealing residues involved in allosteric networks of TIM-barrels and their catalytic domains . Multiple NMR methods have also proven useful in studying the nature of allosteric communication between proteins .