The energy landscape of IUP conformations, the effects of post-translational modifications and their relationship to function. (a) The x-axis depicts the conformational ensemble. Conformations that are geometrically similar lie close to each other. The y-axis depicts the population size. (b) The dynamic conformational selection of IUPs through post-translational modifications and molecular interactions. Here two post-translational modifications are shown: phosphorylation (P) and acetylation (K). Both result in conformational selection and population shift in the ensemble of structures. Many structural clusters coexist for a seemingly unstructured protein. Post-translational modifications create allosteric perturbation sites, propagating through the structures like waves. The observable outcome is a shift in the distribution of the population, biasing the ensemble towards conformers whose structures are favored to bind specific partners. (c) A specific conformation is selected by a binding partner with best complementarity to the IUP binding site.