Evaluating the influence of initial magnetization conditions on extracted exchange parameters in NMR relaxation experiments: applications to CPMG and CEST

[nmrlearner]

Evaluating the influence of initial magnetization conditions on extracted exchange parameters in NMR relaxation experiments: applications to CPMG and CEST

Abstract


Transient excursions of native protein states to functionally relevant higher energy conformations often occur on the μsâ??ms timescale. NMR spectroscopy has emerged as an important tool to probe such processes using techniques such as Carrâ??Purcellâ??Meiboomâ??Gill (CPMG) relaxation dispersion and Chemical Exchange Saturation Transfer (CEST). The extraction of kinetic and structural parameters from these measurements is predicated upon mathematical modeling of the resulting relaxation profiles, which in turn relies on knowledge of the initial magnetization conditions at the start of the CPMG/CEST relaxation elements in these experiments. Most fitting programs simply assume initial magnetization conditions that are given by equilibrium populations, which may be incorrect in certain implementations of experiments. In this study we have quantified the systematic errors in extracted parameters that are generated from analyses of CPMG and CEST experiments using incorrect initial boundary conditions. We find that the errors in exchange rates (k ex ) and populations (p E ) are typically small (