Preprints
https://doi.org/10.5194/mr-2024-7
https://doi.org/10.5194/mr-2024-7
09 Apr 2024
 | 09 Apr 2024
Status: a revised version of this preprint was accepted for the journal MR and is expected to appear here in due course.

Analysis of chi angle distributions in isolated amino acids via multiplet fitting of proton scalar couplings

Nabiha R. Syed, Nafisa B. Masud, and Colin A. Smith

Abstract. Scalar couplings are a fundamental aspect of nuclear magnetic resonance (NMR) experiments and provide rich information about electron-mediated interactions between nuclei. 3J couplings are particularly useful for determining molecular structure through the Karplus relationship, a mathematical formula used for calculating 3J coupling constants from dihedral angles. In small molecules, scalar couplings are often determined through analysis of one-dimensional proton spectra. Larger proteins have typically required specialized multidimensional pulse programs designed to overcome spectral crowding and multiplet complexity. Here we present a generalized framework for fitting scalar couplings with arbitrarily complex multiplet patterns using a weak coupling model. The method is implemented in FitNMR and applicable to 1D, 2D, and 3D NMR spectra. To gain insight into the proton-proton coupling patterns present in protein side chains, we analyze a set of isolated amino acid 1D spectra. We show that the weak-coupling assumption is largely sufficient for fitting the majority of resonances, although there are notable exceptions. To enable structural interpretation of all couplings, we extend a self-consistent Karplus parameterization of side chain chi 1 to chi 2–4. An enhanced model of side chain motion incorporating rotamer statistics from the Protein Data Bank (PDB) is developed. Even without stereospecific assignments of the beta hydrogens, we find that two couplings are sufficient to exclude a single-rotamer model for all amino acids except proline. While most isolated amino acids show rotameric populations consistent with crystal structure statistics, beta-branched valine and isoleucine deviate substantially.

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Nabiha R. Syed, Nafisa B. Masud, and Colin A. Smith

Status: closed

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • CC1: 'Comment on mr-2024-7', Gottfried Otting, 10 Apr 2024
  • RC1: 'Comment on mr-2024-7', Anonymous Referee #1, 15 Apr 2024
  • RC2: 'Comment on mr-2024-7', Anonymous Referee #2, 26 Apr 2024
  • AC1: 'Comment on mr-2024-7', Colin Smith, 17 May 2024

Status: closed

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • CC1: 'Comment on mr-2024-7', Gottfried Otting, 10 Apr 2024
  • RC1: 'Comment on mr-2024-7', Anonymous Referee #1, 15 Apr 2024
  • RC2: 'Comment on mr-2024-7', Anonymous Referee #2, 26 Apr 2024
  • AC1: 'Comment on mr-2024-7', Colin Smith, 17 May 2024
Nabiha R. Syed, Nafisa B. Masud, and Colin A. Smith
Nabiha R. Syed, Nafisa B. Masud, and Colin A. Smith

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Short summary
Scalar couplings give rise to peak splitting in nuclear magnetic resonance (NMR) spectra. Couplings between atoms that span a rotatable bond report on the rotation angle of the bond. Here we describe a new computational method that can be used to analyze complex patterns of peak splitting. In addition to showing new ways of visualizing and analyzing the underlying data, we uncover how isolated parts of proteins behave differently than when they are embedded in a folded protein.