By using an advanced NMR technique, researchers in Germany have taken a closer look at how a protein can alter its structure to bind to different partners (Science 2008, 320, 1471). In the past, it had been difficult to determine the molecular mechanism underlying these conformational changes because researchers had trouble observing protein motions at the right time scales. Now, Christian Griesinger and Bert L. de Groot of the Max Planck Institute for Biophysical Chemistry, in Göttingen, Germany, and colleagues at Vanderbilt University have used NMR to examine a protein's dynamics during the crucial time window when binding takes place. By analyzing internuclear magnetic interactions called residual dipolar couplings, the team obtained a suite of NMR structures that document the flexibility of unbound ubiquitin, a regulatory protein tag. They compared their set of structures with 46 previously published X-ray crystal structures of ubiquitin bound to various partners. They found that the structural changes resulting from the binding interactions are already present in free ubiquitin's fluctuations. The results suggest that ubiquitin continuously shuffles through the different conformations necessary for complex formation, rather than being induced to change conformations upon binding.