Advances in oxygen-17 NMR for biological structure determination
Author(s)
Keeler, Eric George
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Alternative title
Advances in oxygen-17 nuclear magnetic resonance for biological structure determination
Other Contributors
Massachusetts Institute of Technology. Department of Chemistry.
Advisor
Robert G. Griffin.
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The determination of the structures of biological systems, such as, fibril-forming peptides and proteins, membrane proteins, and viruses, by solid-state nuclear magnetic resonance (NMR) spectroscopy has materialized as an important field due to the high-resolution details that the technique provides. While solid-state NMR studies have focused on the three prevalent spin I = 1/2 nuclei present in biomolecules, oxygen has largely been ignored as a probe of the structure of such systems. Described in this thesis are the results of studies to advance the use of solid-state ¹⁷O NMR spectroscopy for structure determination of biological molecules by utilizing the sensitivity of the electric field gradient (EFG) and chemical shift tensors of ¹⁷O. We demonstrated a distinct chemical shift range for bound water in crystalline amino acids and dipeptides and identified discordance between experimental and calculated EFG parameters. This difference was further studied via variable temperature ¹⁷O NMR experiments on barium chlorate monohydrate that demonstrated the effect of the librational motions of the bound water on the NMR measurable ¹⁷O quadrupolar coupling constant. A well resolved splitting in the ¹⁷O magic-angle spinning NMR spectrum was shown at the'rigid lattice limit of the bound water that was determined to be caused by the interaction between the ¹H-¹H dipole coupling and the ¹H-¹⁷O dipole couplings. Further study of bound water environments is presented exhibiting the ability to resolve multiple unique bound water environments in a single system by high-resolution ¹⁷O NMR spectroscopy. We demonstrate the ability to utilize dynamic nuclear polarization (DNP) NMR to polarize multiple nuclei via an endogenous radical dopant that does not disrupt the native crystal structure. Efficient ¹⁷O labeling of a dipeptide is explored to enable the study of the dipeptide via ¹⁷O NMR. Utilizing one- and two-dimensional double resonance correlation spectroscopy, the interatomic correlations between oxygen and carbon, nitrogen, and hydrogen atoms were explored, exhibiting the ability of ¹⁷O NMR to determine structural characteristics of biomolecular solids. A study on the use of DNP NMR to study biosilica entrapped proteins is also presented as part of this thesis.
Description
Thesis: Ph. D. in Physical Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2017. Cataloged from PDF version of thesis. Vita. Includes bibliographical references.
Date issued
2017Department
Massachusetts Institute of Technology. Department of ChemistryPublisher
Massachusetts Institute of Technology
Keywords
Chemistry.