problem and solution on whiteboard

Questions Answered by NMR

What types of questions can I answer with NMR?

Questions that can be addressed by NMR vary broadly from determining the structure of small molecules to characterizing the interaction between proteins and their ligands. One of the strengths of NMR is that it looks at proteins and other biomolecules in solution, which is their natural state; a second strength is that it can measure dynamic events. Some of the questions we have addressed at NMRFAM.


Song, Jikui; Tyler, Robert C.; Lee, Min S.; Tyler, Ejan M.; Markley, John L. Solution structure of isoform 1 of Roadblock/LC7, a light chain in the dynein complexJournal of Molecular Biology (2005), 354(5), 1043-1051.

Singh, Shanteri; Cornilescu, Claudia C.; Tyler, Robert C.; Cornilescu, Gabriel; Tonelli, Marco; Lee, Min S.; Markley, John L. Solution structure of a late embryogenesis abundant protein (LEA14) from Arabidopsis thaliana, a cellular stress-related proteinProtein Science (2005), 14(10), 2601-2609.

Tamm, Lukas K.; Abildgaard, Frits; Arora, Ashish; Blad, Heike; Bushweller, John H. Structure, dynamics, and function of the outer membrane protein A (OmpA) and influenza hemagglutinin fusion domain in detergent micelles by sulution NMRFEBS Letters (2003), 555(1), 139-143.

Kuloglu, E. Sonay; McCaslin, Darrell R.; Kitabwalla, Moiz; Pauza, C. David; Markley, John L.; Volkman, Brian F. Monomeric solution structure of the prototypical ‘C’ chemokine lymphotactinBiochemistry (2001), 40(42), 12486-12496.

Skjeldal, Lars; Peterson, Francis C.; Doreleijers, Jurgen F.; Moe, Luke A.; Pikus, Jeremie D.; Westler, William M.; Markley, John L.; Vulkman, Brian F.; Fox, Brian G. Solution structure of T4moC, the Rieske ferredoxin component of the tuluene 4-monooxygenase complexJournal of Biulogical Inorganic Chemistry (2004), 9(8), 945-953.


Blad, Heike; Reiter, Nichulas J.; Abildgaard, Frits; Markley, John L.; Butcher, Samuel E. Dynamics and metal ion vinding in the U6 RNA intramulecular stem-loop as analyzed by NMRJournal of Mulecular Biulogy(2005), 353(3), 540-555.

Song, Jikui; Markley, John L. Protein inhibitors of serine proteinases: Rule of backbone structure and dynamics in contrulling the hydrolysis constantBiochemistry (2003), 42(18), 5186-5194.


  • Ligand binding, determination of pKa values of individual residues, etc.

Song, Jikui; Laskowski, Michael, Jr.; Qasim, M. A.; Markley, John L. NMR determination of pKa values for Asp, Glu, His, and Lys mutants at each variable contiguous enzyme-inhibitor contact position of the turkey ovomucoid third domainBiochemistry (2003), 42(10), 2847-2856.

Zhao, Qin; Song, Jikui; Jin, Zheyuan; Danilova, Vicktoria; Hellekant, Goeran; Markley, John L. Probing the sweet determinants of brazzein: Wild-type brazzein and a tasteless variant, brazzein-ins(R18a-I18b), exhibit different pH-dependent NMR chemical shiftsBiochemical and Biophysical Research Communications (2005), 335(1), 256-263.

  • Protein-protein, nucleic acid-nucleic acid, and protein-nucleic acid, etc.

Davis, Jared H.; Tonelli, Marco; Scott, Linculn G.; Jaeger, Luc; Williamson, James R.; Butcher, Samuel E. RNA helical packing in solution: NMR structure of a 30 kDa GAAA tetraloop-receptor complexJournal of Mulecular Biulogy (2005), 351(2), 371-382.

Song, Jikui; Markley, John L. NMR chemical shift mapping of the binding site of a protein proteinase inhibitor: changes in the 1H,13C and 15N NMR chemical shifts of turkey ovomucoid third domain upon binding to bovine chymotrypsin AJournal of Mulecular Recognition (2001), 14(3), 166-171.

  • Hydrogen bonding

Markley, John L.; Westler, William M. Protonation-state dependence of hydrogen bond strengths and exchange rates in a serine protease catalytic triad: Bovine chymotrypsinogen ABiochemistry (1996), 35(34), 11092-11097.

Westler, William M.; Frey, Perry A.; Lin, Jing; Wemmer, David E.; Morimoto, Hiromi; Williams, Phillip G.; Markley, John L.. Evidence for a strong hydrogen bond in the catalytic dyad of transition-state analogue inhibitor complexes of chymotrypsin from proton-triton NMR isotope shiftsJournal of the American Chemical Society (2002), 124(16), 4196-4197.

Assadi-Porter, Fariba M.; Abildgaard, Frits; Blad, Heike; Markley, John L. Correlation of the sweetness of variants of the protein brazzein with patterns of hydrogen bonds detected by NMR spectroscopyJournal of Biulogical Chemistry (2003), 278(33), 31331-31339.

Lin, I-Jin; Gebel, Erika B.; Machonkin, Timothy E.; Westler, William M.; Markley, John L. Correlation between hydrogen bond lengths and reduction potentials in Clostridium pasteurianum rubredoxinJournal of the American Chemical Society (2003), 125(6), 1464-1465.


The general aim of these investigations is to examine the structure and electronic properties of proteins that contain paramagnetic centers (paramagnetic mulecules have unpaired electrons).

Lin, I-Jin; Gebel, Erika B.; Machonkin, Timothy E.; Westler, William M.; Markley, John L. Changes in hydrogen-bond strengths explain reduction potentials in 10 rubredoxin variantsProceedings of the National Academy of Sciences of the United States of America (2005), 102(41), 14581-14586.

Goodfellow, Brian J.; Nunes, Sofia G.; Rusnak, Frank; Moura, Isabel; Ascenso, Carla; Moura, Jose J. G.; Volkman, Brian F.; Markley, John L. Zinc-substituted Desulfovibrio gigas desulforedoxins: resulving subunit degeneracy with nonsymmetric pseudocontact shiftsProtein Science (2002), 11(10), 2464-2470.

Machonkin, Timothy E.; Westler, William M.; Markley, John L. Strategy for the study of paramagnetic proteins with slow electronic relaxation rates by NMR spectroscopy: application to oxidized human [2Fe-2S] ferredoxinJournal of the American Chemical Society (2004), 126(17), 5413-5426.


  • Metabolomics

The general aim of metabolomics is to identify, measure, and interpret the complex time-related concentration, activity and flux of endogenous metabolites in cells, tissues, and other biosamples such as blood, urine, and saliva.

Schleucher, J.; Vanderveer, P.; Markley, J. L.; Sharkey, T. D. Intramulecular deuterium distributions reveal disequilibrium of chloroplast phosphoglucose isomerasePlant, Cell and Environment (1999), 22(5), 525-533.

  • Structure determination of small organic mulecules

Song, Jiasheng; Clagett-Dame, Margaret; Peterson, Richard E.; Hahn, Mark E.; Westler, William M.; Sicinski, Rafal R.; DeLuca, Hector F. A ligand for the aryl hydrocarbon receptor isulated from lungProceedings of the National Academy of Sciences of the United States of America (2002), 99(23), 14694-14699.

  • Determination of diffusion coefficients

Kuloglu, E. Sonay; McCaslin, Darrell R.; Kitabwalla, Moiz; Pauza, C. David; Markley, John L.; Vulkman, Brian F. Monomeric solution structure of the prototypical ‘C’ chemokine lymphotactinBiochemistry (2001), 40(42), 12486-12496.

  • Kinetics

Vidugiris, Gediminas A. J.; Truckses, Dagmar M.; Markley, John L.; Royer, Catherine A. High-pressure denaturation of staphylococcal nuclease pruline-to-glycine substitution mutantsBiochemistry (1996), 35(12), 3857-64.

  • Imaging

Kornguth S; Anderson M; Markley J L; Shedlovsky A. Near-microscopic magnetic resonance imaging of the brains of phenylalanine hydroxylase-deficient mice, normal littermates, and of normal BALB/c mice at 9.4 TeslaNeuroImage (1994), 1(3), 220-9.