Abstract
The transverse relaxation rate, R 2, measured as a function of the effective field (R 2 dispersion) using a Carr-Purcell-Meiboom-Gill (CPMG) pulse train, is well suited to detect conformational exchange in proteins. The dispersion data are commonly fitted by a two-site (sites a and b) exchange model with four parameters: the relative population, p a, the difference in chemical shifts of the two sites, δω, the correlation time for exchange, τex, and the intrinsic relaxation rate (i.e., transverse relaxation rate in the absence of chemical exchange), R 02 . Although the intrinsic relaxation rates of the two sites, R 0a2 and R 0b2 , can differ, they are normally assumed to be the same (i.e., R 0a2 = R 0b2 = R 02 ) when fitting dispersion data. The purpose of this investigation is to determine the magnitudes of the errors in the optimized exchange parameters that are introduced by the assumption that R 0a2 = R 0b2 . In order to accomplish this goal, we first generated synthetic constant-time CPMG R 2 dispersion data assuming two-site exchange with R 0a2 ≠ R 0b2 , and then fitted the synthetic data assuming two-site exchange with R 02 = R 0a2 = R 0b2 . Although all the synthetic data generated assuming R 0a2 ≠ R 0b2 were well fitted (assuming R 0a2 = R 0b2 ), the optimized values of p a and τ ex differed from their true values, whereas the optimized values of δω values did not. A theoretical analysis using the Carver–Richards equation explains these results, and yields simple, general equations for estimating the magnitudes of the errors in the optimized parameters, as a function of ( R 0a2 − R 0b2 ).
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Ishima, R., Torchia, D.A. Accuracy of Optimized Chemical-exchange Parameters Derived by Fitting CPMG R 2 Dispersion Profiles when R 0a2 ≠ R 0b2 . J Biomol NMR 34, 209–219 (2006). https://doi.org/10.1007/s10858-005-6226-7
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DOI: https://doi.org/10.1007/s10858-005-6226-7