Chemical Shifts of the Carbohydrate Binding Domain of Galectin-3 from Magic Angle Spinning NMR and Hybrid Quantum Mechanics/Molecular Mechanics Calculations

Research output: Contribution to journalArticle


Magic angle spinning NMR spectroscopy is uniquely suited to probe the structure and dynamics of insoluble proteins and protein assemblies at atomic resolution, with NMR chemical shifts containing rich information about biomolecular structure. Access to this information, however, is problematic, since accurate quantum mechanical calculation of chemical shifts in proteins remains challenging, particularly for 15NH. Here we report on isotropic chemical shift predictions for the carbohydrate recognition domain of microcrystalline galectin-3, obtained from using hybrid quantum mechanics/molecular mechanics (QM/MM) calculations, implemented using an automated fragmentation approach, and using very high resolution (0.86 Å lactose-bound and 1.25 Å apo form) X-ray crystal structures. The resolution of the X-ray crystal structure used as an input into the AF-NMR program did not affect the accuracy of the chemical shift calculations to any significant extent. Excellent agreement between experimental and computed shifts is obtained for 13Cα, while larger scatter is observed for 15NH chemical shifts, which are influenced to a greater extent by electrostatic interactions, hydrogen bonding, and solvation.


  • Jodi Kraus
  • Rupal Gupta
  • Jenna Yehl
  • Manman Lu
  • David A. Case
  • Angela M. Gronenborn
  • Mikael Akke
  • Tatyana Polenova
External organisations
  • University of Delaware
  • University of Pittsburgh
  • Rutgers University: The State University of New Jersey
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Physical Chemistry
Original languageEnglish
Pages (from-to)2931-2939
Number of pages9
JournalJournal of Physical Chemistry B
Issue number11
Publication statusPublished - 2018 Mar 22
Publication categoryResearch