Detecting anisotropic segmental dynamics in disordered proteins by cross-correlated spin relaxation.

Among the numerous contributions of Geoffrey Bodenhausen to NMR spectroscopy, his developments in the field of spin-relaxation methodology and theory will definitely have a long lasting impact. Starting with his seminal contributions to the excitation of multiple-quantum coherences, he and his group thoroughly investigated the intricate relaxation properties of these "forbidden fruits" and developed experimental techniques to reveal the relevance of previously largely ignored cross-correlated relaxation (CCR) effects, as "the essential is invisible to the eyes". Here we consider CCR within the challenging context of intrinsically disordered proteins (IDPs) and emphasize its potential and relevance for the studies of structural dynamics of IDPs in the future years to come. Conventionally, dynamics of globularly folded proteins are modeled and understood as deviations from otherwise rigid structures tumbling in solution. However, with increasing protein flexibility, as observed for IDPs, this apparent dichotomy between structure and dynamics becomes blurred. Although complex dynamics and ensemble averaging might impair the extraction of mechanistic details even further, spin relaxation uniquely encodes a protein's structural memory. Due to significant methodological developments, such as high-dimensional non-uniform sampling techniques, spin relaxation in IDPs can now be monitored in unprecedented resolution. Not embedded within a rigid globular fold, conventional