Probingthe Broad Time Scale and Heterogeneous ConformationalDynamics in the Catalytic Core of the Arf-GAP ASAP1 via Methyl AdiabaticRelaxation Dispersion

Methyl-TROSY is one of the most powerful NMR spectroscopic tools for studying structures and conformational dynamics of large protein complexes in solution. In studying conformational dynamics, side-chains usually display heterogeneous dynamics, including col-lective and local motions, that can be difficult to detect and analyze by conventional relaxation dispersion (RD) approaches. The combi-nation of NH-based adiabatic relaxation dispersion experiments and geometric approximation (geoHARD) has been shown to have sev-eral advantages over conventional RD to reveal conformational dynamics over a broad timescale. Here, we demonstrate a new technique developed to detect both heterogeneous and wide timescale conformational dynamics in the hydrophobic interior of large macro-molecules utilizing methyl-geoHARD. It is shown that methyl-geoHARD will be feasible at ultra-high magnetic fields (> 1 GHz), when this technology becomes available. For the ZA domain of the Arf-GAP ASAP1, with a global correlational time ...