Existence of Singularities in NMR Relaxation Dispersion Profiles: Implications for Hidden Dynamics.

It is common for NMR relaxation dispersion experiments to suggest an absence of dynamics despite anecdotal indications of conformational dynamics. We explore the potential explanations and approaches to this conundrum. Some inconsistencies have been observed between two relaxation dispersion experiments, Carr-Purcell-Meiboom-Gill (CPMG) and adiabatic relaxation dispersion experiments, in recent dynamic studies of different biomolecules. Theoretical analyses show that such seemingly paradoxical results might come from a complex exchange topology that is concealed by the application of the simple two-site exchange model for interpretation of the relaxation dispersion data. Scenarios are explored and revealed in which the presence of complex millisecond conformational exchange could suppress the amplitude of CPMG relaxation dispersion profiles, even when the exchange rates are within the detectable range of the experiments. With experimental errors, the suppressed relaxation dispersion profiles could lead to the conclusion of "no millisecond conformational exchange". However, such hidden dynamics can potentially be detected by adiabatic relaxation dispersion experiments. Finally, we demonstrate some advantages of adiabatic relaxation dispersion experiments over conventional relaxation dispersion experiments and a simplified computational approach to analyze the adiabatic relaxation dispersion profiles.