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

Kraus, Jodi; Gupta, Rupal; Yehl, Jenna; Lu, Manman; Case, David A.; Gronenborn, Angela M.; Akke, Mikael LU and Polenova, Tatyana (2018) In Journal of Physical Chemistry B 122(11). p.2931-2939
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physical Chemistry B
volume
122
issue
11
pages
9 pages
publisher
The American Chemical Society
external identifiers
  • scopus:85044274356
ISSN
1520-6106
DOI
10.1021/acs.jpcb.8b00853
language
English
LU publication?
yes
id
8fc61af9-dc99-4767-adb9-7c3db53445cb
date added to LUP
2018-04-03 14:43:22
date last changed
2019-03-17 05:04:59
@article{8fc61af9-dc99-4767-adb9-7c3db53445cb,
  abstract     = {<p>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 <sup>15</sup>N<sup>H</sup>. 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 <sup>13</sup>C<sup>α</sup>, while larger scatter is observed for <sup>15</sup>N<sup>H</sup> chemical shifts, which are influenced to a greater extent by electrostatic interactions, hydrogen bonding, and solvation.</p>},
  author       = {Kraus, Jodi and Gupta, Rupal and Yehl, Jenna and Lu, Manman and Case, David A. and Gronenborn, Angela M. and Akke, Mikael and Polenova, Tatyana},
  issn         = {1520-6106},
  language     = {eng},
  month        = {03},
  number       = {11},
  pages        = {2931--2939},
  publisher    = {The American Chemical Society},
  series       = {Journal of Physical Chemistry B},
  title        = {Chemical Shifts of the Carbohydrate Binding Domain of Galectin-3 from Magic Angle Spinning NMR and Hybrid Quantum Mechanics/Molecular Mechanics Calculations},
  url          = {http://dx.doi.org/10.1021/acs.jpcb.8b00853},
  volume       = {122},
  year         = {2018},
}