The populations of the trans, gauche(-), and gauche(+) χ 1 conformers derived from the experimental J-couplings 64 are 21, 32, and 47%, respectively (Table ), indicating a highly mobile side chain that populates all possible states. In contrast, in the MD simulations, the χ 1 dihedral angle of ILE3 exclusively adopts the gauche(+) conformation, irrespective of the force field. This may be a kinetic trapping effect, as this conformer is also present at the start of the simulations (Table , last column). Interestingly, the CCR rates of both methyl groups, ILE3-C γ,2 and ILE3-C δ , are quite fast (> 2.5 s -1 ), and the CCR rates from the MD simulations are in good agreement with the experimental values. For ILE3-C γ,2 , the CCR rates are 2.81 and 2.59 s -1 with AMBER and CHARMM36, respectively, compared to 2.77 s -1 in NMR; for ILE3-C δ , the MD rates of 2.57 and 2.01 s -1 are also in reasonable agreement with the experimental CCR rate of 2.51 s -1 (see Table ). Furthermore, the experimental methyl axis order parameters are 0.92 and 0.80 for ILE3-C γ,2 and ILE3-C δ , respectively (Table ), further supporting the notion that the ILE3 side chain is actually rather rigid. These seeming discrepancies are resolved when comparing the methyl axis order parameter of ILE3-C γ,2 obtained from dipolar couplings, S 2 D = 0.38, to the one from relaxation (0.92). S 2 D measures the order parameter on much slower time scales than the ones probed by relaxation, and hence it captures contributions from slow rotamer averaging beyond the rotational correlation time. In summary, the rotamer averaging of the ILE3 side chain is indeed incomplete in the MD simulations, but that does not affect the computed CCR rates in this case because the dynamics that are missed happen on the supra-τ c time scale and are thus not captured in the relaxation experiments.