Preprints
https://doi.org/10.5194/mr-2021-60
https://doi.org/10.5194/mr-2021-60

  02 Sep 2021

02 Sep 2021

Review status: this preprint is currently under review for the journal MR.

Analysis of Conformational Exchange Processes using Methyl-TROSY-Based Hahn Echo Measurements of Quadruple-Quantum Relaxation

Christopher Andrew Waudby1 and John Christodoulou1,2 Christopher Andrew Waudby and John Christodoulou
  • 1Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK
  • 2Francis Crick Institute, London NW1 1AT, UK

Abstract. Transverse nuclear spin relaxation is a sensitive probe of chemical exchange on timescales on the order of microseconds to milliseconds. Here we present an experiment for the simultaneous measurement of the relaxation rates of two quadruple-quantum transitions in 13CH3-labelled methyl groups. These coherences are protected against relaxation by intra-methyl dipolar interactions, and so have unexpectedly long lifetimes within perdeuterated biomacromolecules. However, these coherences also have an order of magnitude higher sensitivity to chemical exchange broadening than lower order coherences, and therefore provide ideal probes of dynamic processes. We show that analysis of the static magnetic field dependence of zero-, double- and quadruple-quantum Hahn echo relaxation rates provides a robust indication of chemical exchange, and can determine the signed relative magnitudes of proton and carbon chemical shift differences between ground and excited states. We also demonstrate that this analysis can be combined with established CPMG relaxation dispersion measurements, providing improved precision in parameter estimates, particularly in the determination of 1H chemical shift differences.

Christopher Andrew Waudby and John Christodoulou

Status: open (until 30 Sep 2021)

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • RC1: 'Comment on mr-2021-60', Anonymous Referee #1, 08 Sep 2021 reply
    • AC1: 'Reply on RC1', Chris Waudby, 13 Sep 2021 reply

Christopher Andrew Waudby and John Christodoulou

Christopher Andrew Waudby and John Christodoulou

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Short summary
We describe a suite of experiments that exploit field-dependent relaxation measurements of four spin transitions in methyl groups to characterise chemical exchange processes, and which can be used as an alternative or complement to CPMG relaxation dispersion measurements. We show that these four spin transitions benefit from the methyl TROSY effect, and so provide a unique combination of slow intrinsic relaxation and high sensitivity to chemical exchange.