Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 312 (5771): 224-228

Copyright © 2006 by the American Association for the Advancement of Science

New Tools Provide New Insights in NMR Studies of Protein Dynamics

Anthony Mittermaier1, and Lewis E. Kay2

Abstract: There is growing evidence that structural flexibility plays a central role in the function of protein molecules. Many of the experimental data come from nuclear magnetic resonance (NMR) spectroscopy, a technique that allows internal motions to be probed with exquisite time and spatial resolution. Recent methodological advancements in NMR have extended our ability to characterize protein dynamics and promise to shed new light on the mechanisms by which these molecules function. Here, we present a brief overview of some of the new methods, together with applications that illustrate the level of detail at which protein motions can now be observed.

1 Department of Chemistry, McGill University, Montreal, Quebec H3A 2K6, Canada. E-mail: anthony.mittermaier{at}
2 Department of Medical Genetics, Department of Biochemistry, and Department of Chemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. E-mail: kay{at}

Evidence of Ternary Complex Formation in Trypanosoma cruzi trans-Sialidase Catalysis.
I. A. Oliveira, A. S. Goncalves, J. L. Neves, M. von Itzstein, and A. R. Todeschini (2014)
J. Biol. Chem. 289, 423-436
   Abstract »    Full Text »    PDF »
Mechanism of E-cadherin dimerization probed by NMR relaxation dispersion.
Y. Li, N. L. Altorelli, F. Bahna, B. Honig, L. Shapiro, and A. G. Palmer III (2013)
PNAS 110, 16462-16467
   Abstract »    Full Text »    PDF »
The allosteric communication pathways in KIX domain of CBP.
F. Palazzesi, A. Barducci, M. Tollinger, and M. Parrinello (2013)
PNAS 110, 14237-14242
   Abstract »    Full Text »    PDF »
ShereKhan--calculating exchange parameters in relaxation dispersion data from CPMG experiments.
A. Mazur, B. Hammesfahr, C. Griesinger, D. Lee, and M. Kollmar (2013)
Bioinformatics 29, 1819-1820
   Abstract »    Full Text »    PDF »
Towards physiological complexity with in vitro single-molecule biophysics.
D. Duzdevich and E. C. Greene (2012)
Phil Trans R Soc B 368, 20120271
   Abstract »    Full Text »    PDF »
Folding of the four-helix bundle FF domain from a compact on-pathway intermediate state is governed predominantly by water motion.
A. Sekhar, P. Vallurupalli, and L. E. Kay (2012)
PNAS 109, 19268-19273
   Abstract »    Full Text »    PDF »
Alternative ground states enable pathway switching in biological electron transfer.
L. A. Abriata, D. Alvarez-Paggi, G. N. Ledesma, N. J. Blackburn, A. J. Vila, and D. H. Murgida (2012)
PNAS 109, 17348-17353
   Abstract »    Full Text »    PDF »
Domain-domain interactions in full-length p53 and a specific DNA complex probed by methyl NMR spectroscopy.
M. Bista, S. M. Freund, and A. R. Fersht (2012)
PNAS 109, 15752-15756
   Abstract »    Full Text »    PDF »
Conformational Selection and Substrate Binding Regulate the Monomer/Dimer Equilibrium of the C-terminal domain of Escherichia coli Enzyme I.
V. Venditti and G. M. Clore (2012)
J. Biol. Chem. 287, 26989-26998
   Abstract »    Full Text »    PDF »
Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR.
M. J. Knight, A. J. Pell, I. Bertini, I. C. Felli, L. Gonnelli, R. Pierattelli, T. Herrmann, L. Emsley, and G. Pintacuda (2012)
PNAS 109, 11095-11100
   Abstract »    Full Text »    PDF »
Interdomain dynamics and coactivation of the mRNA decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan.
S. N. Floor, M. S. Borja, and J. D. Gross (2012)
PNAS 109, 2872-2877
   Abstract »    Full Text »    PDF »
Flexibility and binding affinity in protein-ligand, protein-protein and multi-component protein interactions: limitations of current computational approaches.
P. Tuffery and P. Derreumaux (2012)
J R Soc Interface 9, 20-33
   Abstract »    Full Text »    PDF »
Structure and dynamics of a conformationally constrained nitroxide side chain and applications in EPR spectroscopy.
M. R. Fleissner, M. D. Bridges, E. K. Brooks, D. Cascio, T. Kalai, K. Hideg, and W. L. Hubbell (2011)
PNAS 108, 16241-16246
   Abstract »    Full Text »    PDF »
Accessing protein conformational ensembles using room-temperature X-ray crystallography.
J. S. Fraser, H. van den Bedem, A. J. Samelson, P. T. Lang, J. M. Holton, N. Echols, and T. Alber (2011)
PNAS 108, 16247-16252
   Abstract »    Full Text »    PDF »
Molecular Evolution of Protein Conformational Changes Revealed by a Network of Evolutionarily Coupled Residues.
J. Jeon, H.-J. Nam, Y. S. Choi, J.-S. Yang, J. Hwang, and S. Kim (2011)
Mol. Biol. Evol. 28, 2675-2685
   Abstract »    Full Text »    PDF »
Dynamic fluctuations lubricate the circadian clock.
M.-T. Pai and C. Kalodimos (2011)
PNAS 108, 14377-14378
   Full Text »    PDF »
Catalysis by dihydrofolate reductase and other enzymes arises from electrostatic preorganization, not conformational motions.
A. J. Adamczyk, J. Cao, S. C. L. Kamerlin, and A. Warshel (2011)
PNAS 108, 14115-14120
   Abstract »    Full Text »    PDF »
A Dynamic Knockout Reveals That Conformational Fluctuations Influence the Chemical Step of Enzyme Catalysis.
G. Bhabha, J. Lee, D. C. Ekiert, J. Gam, I. A. Wilson, H. J. Dyson, S. J. Benkovic, and P. E. Wright (2011)
Science 332, 234-238
   Abstract »    Full Text »    PDF »
High-pressure EPR reveals conformational equilibria and volumetric properties of spin-labeled proteins.
J. McCoy and W. L. Hubbell (2011)
PNAS 108, 1331-1336
   Abstract »    Full Text »    PDF »
Appropriation of the MinD protein-interaction motif by the dimeric interface of the bacterial cell division regulator MinE.
H. Ghasriani, T. Ducat, C. T. Hart, F. Hafizi, N. Chang, A. Al-Baldawi, S. H. Ayed, P. Lundstrom, J.-A. R. Dillon, and N. K. Goto (2010)
PNAS 107, 18416-18421
   Abstract »    Full Text »    PDF »
Atomic-Level Characterization of the Structural Dynamics of Proteins.
D. E. Shaw, P. Maragakis, K. Lindorff-Larsen, S. Piana, R. O. Dror, M. P. Eastwood, J. A. Bank, J. M. Jumper, J. K. Salmon, Y. Shan, et al. (2010)
Science 330, 341-346
   Abstract »    Full Text »    PDF »
Structural Basis for Capping Protein Sequestration by Myotrophin (V-1).
A. Zwolak, I. Fujiwara, J. A. Hammer III, and N. Tjandra (2010)
J. Biol. Chem. 285, 25767-25781
   Abstract »    Full Text »    PDF »
Two-dimensional NMR and All-atom Molecular Dynamics of Cytochrome P450 CYP119 Reveal Hidden Conformational Substates.
J. N. Lampe, R. Brandman, S. Sivaramakrishnan, and P. R. O. de Montellano (2010)
J. Biol. Chem. 285, 9594-9603
   Abstract »    Full Text »    PDF »
NMR analysis of G-protein {beta}{gamma} subunit complexes reveals a dynamic G{alpha}-G{beta}{gamma} subunit interface and multiple protein recognition modes.
A. V. Smrcka, N. Kichik, T. Tarrago, M. Burroughs, M.-S. Park, N. K. Itoga, H. A. Stern, B. M. Willardson, and E. Giralt (2010)
PNAS 107, 639-644
   Abstract »    Full Text »    PDF »
Domain-elongation NMR spectroscopy yields new insights into RNA dynamics and adaptive recognition.
Q. Zhang and H. M. Al-Hashimi (2009)
RNA 15, 1941-1948
   Abstract »    Full Text »    PDF »
Transient structural distortion of metal-free Cu/Zn superoxide dismutase triggers aberrant oligomerization.
K. Teilum, M. H. Smith, E. Schulz, L. C. Christensen, G. Solomentsev, M. Oliveberg, and M. Akke (2009)
PNAS 106, 18273-18278
   Abstract »    Full Text »    PDF »
The intrinsic dynamics of enzymes plays a dominant role in determining the structural changes induced upon inhibitor binding.
A. Bakan and I. Bahar (2009)
PNAS 106, 14349-14354
   Abstract »    Full Text »    PDF »
Conformational selection or induced fit: A flux description of reaction mechanism.
G. G. Hammes, Y.-C. Chang, and T. G. Oas (2009)
PNAS 106, 13737-13741
   Abstract »    Full Text »    PDF »
Constructing RNA dynamical ensembles by combining MD and motionally decoupled NMR RDCs: new insights into RNA dynamics and adaptive ligand recognition.
A. T. Frank, A. C. Stelzer, H. M. Al-Hashimi, and I. Andricioaei (2009)
Nucleic Acids Res. 37, 3670-3679
   Abstract »    Full Text »    PDF »
Sending Signals Dynamically.
R. G. Smock and L. M. Gierasch (2009)
Science 324, 198-203
   Abstract »    Full Text »    PDF »
BIOCHEMISTRY: How Do Proteins Interact?.
D. D. Boehr and P. E. Wright (2008)
Science 320, 1429-1430
   Abstract »    Full Text »    PDF »
Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution.
O. F. Lange, N.-A. Lakomek, C. Fares, G. F. Schroder, K. F. A. Walter, S. Becker, J. Meiler, H. Grubmuller, C. Griesinger, and B. L. de Groot (2008)
Science 320, 1471-1475
   Abstract »    Full Text »    PDF »
Interconversion between two unrelated protein folds in the lymphotactin native state.
R. L. Tuinstra, F. C. Peterson, S. Kutlesa, E. S. Elgin, M. A. Kron, and B. F. Volkman (2008)
PNAS 105, 5057-5062
   Abstract »    Full Text »    PDF »
Reassessing a sparse energetic network within a single protein domain.
C. N. Chi, L. Elfstrom, Y. Shi, T. Snall, A. Engstrom, and P. Jemth (2008)
PNAS 105, 4679-4684
   Abstract »    Full Text »    PDF »
Efficient coupling of catalysis and dynamics in the E1 component of Escherichia coli pyruvate dehydrogenase multienzyme complex.
S. Kale, G. Ulas, J. Song, G. W. Brudvig, W. Furey, and F. Jordan (2008)
PNAS 105, 1158-1163
   Abstract »    Full Text »    PDF »
Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy.
S.-T. D. Hsu, P. Fucini, L. D. Cabrita, H. Launay, C. M. Dobson, and J. Christodoulou (2007)
PNAS 104, 16516-16521
   Abstract »    Full Text »    PDF »
Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain.
J. M. Murphy, D. M. Korzhnev, D. F. Ceccarelli, D. J. Briant, A. Zarrine-Afsar, F. Sicheri, L. E. Kay, and T. Pawson (2007)
PNAS 104, 14336-14341
   Abstract »    Full Text »    PDF »
Protein folding and unfolding studied at atomic resolution by fast two-dimensional NMR spectroscopy.
P. Schanda, V. Forge, and B. Brutscher (2007)
PNAS 104, 11257-11262
   Abstract »    Full Text »    PDF »
Intramolecular domain-domain association/dissociation and phosphoryl transfer in the mannitol transporter of Escherichia coli are not coupled.
J.-Y. Suh, J. Iwahara, and G. M. Clore (2007)
PNAS 104, 3153-3158
   Abstract »    Full Text »    PDF »
Solution Structure and Backbone Dynamics of an Endopeptidase HycI from scherichia coli: IMPLICATIONS FOR MECHANISM OF THE [NiFe] HYDROGENASE MATURATION.
F. Yang, W. Hu, H. Xu, C. Li, B. Xia, and C. Jin (2007)
J. Biol. Chem. 282, 3856-3863
   Abstract »    Full Text »    PDF »
Solution Structures and Backbone Dynamics of a Flavodoxin MioC from Escherichia coli in both Apo- and Holo-forms: IMPLICATIONS FOR COFACTOR BINDING AND ELECTRON TRANSFER.
Y. Hu, Y. Li, X. Zhang, X. Guo, B. Xia, and C. Jin (2006)
J. Biol. Chem. 281, 35454-35466
   Abstract »    Full Text »    PDF »
Biochemistry. Enzyme motions inside and out..
S. J. Benkovic and S. Hammes-Schiffer (2006)
Science 312, 208-209
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882