Flexibility and plasticity allow proteins to bind to ligands, form oligomers, aggregate, and perform mechanical work. Large conformational changes in proteins play an important role in cellular signaling. Adenylate Kinase is a signal transducing protein; thus, the balance between conformations regulates protein activity. ADK has a locally unfolded state that becomes depopulated upon binding.
A 2007 study by Whitford et al. shows the conformations of ADK when binding with ATP or AMP. The study shows that there are three relevant conformations or structures of ADK—CORE, Open, and Closed. In ADK, there are two small domains called the LID and NMP. ATP binds in the pocket formed by the LID and CORE domains. AMP binds in the pocket formed by the NMP and CORE domains.  The Whitford study also reported findings that show that localized regions of a protein unfold during conformational transitions. This mechanism reduces the strain and enhances catalytic efficiency. Local unfolding is the result of competing strain energies in the protein.
The local (thermodynamic) stability of the substrate-binding domains ATP and AMP has been shown to be significantly lower when compared with the CORE domain in ADK. Furthermore, it has been shown that the two subdomains (ATP and AMP) can fold and unfold in a "non-cooperative manner." Binding of the substrates causes preference for closed conformations amongst those that are sampled by ADK. These closed conformations are hypothesized to help with removal of water from the active site to avoid wasteful hydrolysis of ATP in addition to helping optimize alignment of substrates for phosphoryl-transfer.  Furthermore, it has been shown that the apoenzyme will still sample the closed conformations of the ATP and AMP domains in the absence of substrates. When comparing the rate of opening of the enzyme (which allows for product release) and the rate of closing that accompanies substrate binding, closing was found to be the slower process.