Intrinsic dynamics of enzymes in the unbound state and relation to allosteric regulation
Open accessAbstract
In recent years, there has been a surge in the number of studies exploring the relationship between proteins' equilibrium dynamics and structural changes involved in function. An emerging concept, supported by both theory and experiments, is that under native state conditions proteins have an intrinsic ability to sample conformations that meet functional requirements. A typical example is the ability of enzymes to sample open and closed forms, irrespective of substrate, succeeded by the stabilization of one form (usually closed) upon substrate binding. This ability is structure-encoded, and plays a key role in facilitating allosteric regulation, which suggests complementing the sequence-encodes-structure paradigm of protein science by structure-encodes-dynamics-encodes-function. The emerging connection implies an evolutionary role in selecting/conserving structures based on their ability to achieve functional dynamics, and in turn, selecting sequences that fold into such 'apt' structures.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Elastic network models have demonstrated the significance of soft collective modes of motion in enabling allosteric regulation of protein systems.
“Bahar and coworkers reviewed approaches based on elastic network models (ENMs), which have demonstrated the significance of soft collective modes of motion in enabling allosteric regulation of protein systems (Bahar et al., 2007, 2017).”
From Allostery in Its Many Disguises: From Theory to Applications (2019) · cites this paper as Bahar et al., 2007
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
Monod, J., Wyman, J., & Changeux, J. (1965) · Journal of Molecular Biology · doi:10.1016/s0022-2836(65)80285-6 · Cited by 7,681 · see citing works
Comparison of Experimental Binding Data and Theoretical Models in Proteins Containing Subunits *
Koshland, D. E., Némethy, G., & Filmer, D. (1966) · Biochemistry · doi:10.1021/bi00865a047 · Cited by 3,019 · see citing works
Application of a Theory of Enzyme Specificity to Protein Synthesis.
Koshland, D. (1958) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.44.2.98 · Cited by 2,140 · see citing works
Evolutionarily Conserved Pathways of Energetic Connectivity in Protein Families
Lockless, S. W., & Ranganathan, R. (1999) · Science · doi:10.1126/science.286.5438.295 · Cited by 1,288 · see citing works
A Perspective on Enzyme Catalysis
Benkovic, S. J., & Hammes‐Schiffer, S. (2003) · Science · doi:10.1126/science.1085515 · Cited by 1,281 · see citing works
Intrinsic dynamics of an enzyme underlies catalysis
Eisenmesser, E., Millet, Ó., Labeikovsky, W., Korzhnev, D., Wolf-Watz, M., Bosco, D. A., Skalicky, J., Kay, L., & Kern, D. (2005) · Nature · doi:10.1038/nature04105 · Cited by 1,057 · see citing works
Conformational change of proteins arising from normal mode calculations
Tama, F., & Sanejouand, Y. (2001) · Protein Engineering Design and Selection · doi:10.1093/protein/14.1.1 · Cited by 895 · see citing works
Is allostery an intrinsic property of all dynamic proteins?
Gunasekaran, K., Ma, B., & Nussinov, R. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20232 · Cited by 882 · see citing works
Allosteric Mechanisms of Signal Transduction
Changeux, J., & Edelstein, S. J. (2005) · Science · doi:10.1126/science.1108595 · Cited by 744 · see citing works
Coarse-grained normal mode analysis in structural biology
Bahar, İ., & Rader, A. J. (2005) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2005.08.007 · Cited by 732 · see citing works
Self-citationAntibody Multispecificity Mediated by Conformational Diversity
James, L. C., Roversi, P., & Tawfik, D. S. (2003) · Science · doi:10.1126/science.1079731 · Cited by 719 · see citing works
The role of dynamics in allosteric regulation
Kern, D., & Zuiderweg, E. R. P. (2003) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2003.10.008 · Cited by 653 · see citing works
Emergence of Preferred Structures in a Simple Model of Protein Folding
Li, H., Helling, R. C., Tang, C., & Wingreen, N. S. (1996) · Science · doi:10.1126/science.273.5275.666 · Cited by 650 · see citing works
Dynamically driven protein allostery
Popovych, N., Sun, S., Ebright, R. H., & Kalodimos, C. G. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1132 · Cited by 637 · see citing works
Relating Protein Motion to Catalysis
Hammes‐Schiffer, S., & Benkovic, S. J. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142800 · Cited by 610 · see citing works
Network of coupled promoting motions in enzyme catalysis
Agarwal, P. K., Billeter, S. R., Rajagopalan, P. T. R., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052005999 · Cited by 461 · see citing works
Multiple diverse ligands binding at a single protein site: A matter of pre‐existing populations
Ma, B., Shatsky, M., Wolfson, H. J., & Nussinov, R. (2002) · Protein Science · doi:10.1110/ps.21302 · Cited by 420 · see citing works
Tobi, D., & Bahar, İ. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507603102 · Cited by 380 · see citing works
Self-citationTama, F., Valle, M., Frank, J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1632476100 · Cited by 345 · see citing works
Frauenfelder, H., McMahon, B. H., Austin, R. H., Chu, K., & Groves, J. T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.041614298 · Cited by 338 · see citing works
Anchor residues in protein–protein interactions
Rajamani, D., Thiel, S., Vajda, S., & Camacho, C. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401942101 · Cited by 334 · see citing works
Ligand binding and internal equilibiums in proteins
Weber, G. (1972) · Biochemistry · doi:10.1021/bi00755a028 · Cited by 329 · see citing works
Anisotropic network model: systematic evaluation and a new web interface
Eyal, E., Yang, L., & Bahar, İ. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl448 · Cited by 324 · see citing works
Self-citationOkazaki, K.-I., Koga, N., Takada, S., Onuchic, J. N., & Wolynes, P. G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604375103 · Cited by 315 · see citing works
The changing landscape of protein allostery
Swain, J. F., & Gierasch, L. M. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.01.003 · Cited by 296 · see citing works
Dynamical Contributions to Enzyme Catalysis: Critical Tests of A Popular Hypothesis
Olsson, M. H. M., Parson, W. W., & Warshel, A. (2006) · Chemical Reviews · doi:10.1021/cr040427e · Cited by 289 · see citing works
Global ribosome motions revealed with elastic network model
Wang, Y., Rader, A. J., Bahar, İ., & Jernigan, R. L. (2004) · Journal of Structural Biology · doi:10.1016/j.jsb.2004.01.005 · Cited by 284 · see citing works
Self-citationYang, L.-W., & Bahar, I. (2005) · Structure · doi:10.1016/j.str.2005.03.015 · Cited by 273 · see citing works
Self-citation(2005) · Chapman & Hall/CRC eBooks · doi:10.1201/9781420035070 · Cited by 266 · see citing works
SYMMETRY, FORM, AND SHAPE: Guiding Principles for Robustness in Macromolecular Machines
Tama, F., & Brooks, C. L. (2006) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.35.040405.102010 · Cited by 266 · see citing works
Natural-like function in artificial WW domains
Russ, W. P., Lowery, D. M., Mishra, P., Yaffe, M. B., & Ranganathan, R. (2005) · Nature · doi:10.1038/nature03990 · Cited by 260 · see citing works
Signal Propagation in Proteins and Relation to Equilibrium Fluctuations
Chennubhotla, C., & Bahar, İ. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030172 · Cited by 230 · see citing works
Self-citationIntramolecular Signaling Pathways Revealed by Modeling Anisotropic Thermal Diffusion
Ota, N., & Agard, D. A. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.05.043 · Cited by 227 · see citing works
Role of Protein Dynamics in Reaction Rate Enhancement by Enzymes
Agarwal, P. K. (2005) · Journal of the American Chemical Society · doi:10.1021/ja055251s · Cited by 211 · see citing works
Xu, C., Tobi, D., & Bahar, İ. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.08.027 · Cited by 198 · see citing works
Self-citationNormal Mode Analysis Suggests a Quaternary Twist Model for the Nicotinic Receptor Gating Mechanism
Taly, A., Delarue, M. H., Grütter, T., Nilges, M., Novère, N. G. L., Corringer, P., & Changeux, J. (2005) · Biophysical Journal · doi:10.1529/biophysj.104.050229 · Cited by 189 · see citing works
Complementarity of Structure Ensembles in Protein-Protein Binding
Grünberg, R., Leckner, J., & Nilges, M. (2004) · Structure · doi:10.1016/j.str.2004.09.014 · Cited by 182 · see citing works
Allostery in a Coarse-Grained Model of Protein Dynamics
Ming, D., & Wall, M. E. (2005) · Physical Review Letters · doi:10.1103/physrevlett.95.198103 · Cited by 165 · see citing works
Allosteric signaling of ATP hydrolysis in GroEL–GroES complexes
Ranson, N. A., Clare, D. K., Farr, G. W., Houldershaw, D., Horwich, A. L., & Saibil, H. R. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1046 · Cited by 152 · see citing works
Markov propagation of allosteric effects in biomolecular systems: application to GroEL–GroES
Chennubhotla, C., & Bahar, İ. (2006) · Molecular Systems Biology · doi:10.1038/msb4100075 · Cited by 151 · see citing works
Self-citationHorn̆ák, V., Okur, A., Rizzo, R. C., & Simmerling, C. L. (2006) · Journal of the American Chemical Society · doi:10.1021/ja058211x · Cited by 106 · see citing works
Formaneck, M. S., Ma, L., & Cui, Q. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20893 · Cited by 106 · see citing works
Switched or Not?: the Structure of Unphosphorylated CheY Bound to the N Terminus of FliM
Dyer, C. M., & Dahlquist, F. W. (2006) · Journal of Bacteriology · doi:10.1128/jb.00637-06 · Cited by 98 · see citing works
Liu, H., & Warshel, A. (2007) · Biochemistry · doi:10.1021/bi700201w · Cited by 96 · see citing works
James, L. C., & Tawfik, D. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500909102 · Cited by 93 · see citing works
Temiz, N. A., Meirovitch, E., & Bahar, İ. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20226 · Cited by 92 · see citing works
Self-citationCommon Mechanism of Pore Opening Shared by Five Different Potassium Channels
Shrivastava, I. H., & Bahar, İ. (2006) · Biophysical Journal · doi:10.1529/biophysj.105.080093 · Cited by 91 · see citing works
Self-citationLou, H., & Cukier, R. I. (2006) · The Journal of Physical Chemistry B · doi:10.1021/jp064303c · Cited by 84 · see citing works
Mechanochemical Coupling in the Myosin Motor Domain. II. Analysis of Critical Residues
Yu, H. B., Ma, L., Yang, Y., & Cui, Q. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030023 · Cited by 82 · see citing works
Trylska, J., Tozzini, V., Chang, C. A., et al. (2007) · Biophysical Journal · doi:10.1529/biophysj.106.100560 · Cited by 78 · see citing works
Structure and Dynamics of Pin1 During Catalysis by NMR
Labeikovsky, W., Eisenmesser, E. Z., Bosco, D. A., & Kern, D. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.01.049 · Cited by 74 · see citing works
Functional residues serve a dominant role in mediating the cooperativity of the protein ensemble
Liu, T., Whitten, S. T., & Hilser, V. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607132104 · Cited by 66 · see citing works
A New Perspective on Response Regulator Activation
Stock, A., & Guhaniyogi, J. (2006) · Journal of Bacteriology · doi:10.1128/jb.01268-06 · Cited by 65 · see citing works
Coupling of Global and Local Vibrational Modes in Dynamic Allostery of Proteins
Hawkins, R. J., & McLeish, T. C. B. (2006) · Biophysical Journal · doi:10.1529/biophysj.106.082180 · Cited by 63 · see citing works
The Signaling Pathway of Rhodopsin
Kong, Y., & Karplus, M. (2007) · Structure · doi:10.1016/j.str.2007.04.002 · Cited by 60 · see citing works
Field, M. J. (2007) · Cambridge University Press eBooks · doi:10.1017/cbo9780511619076.010 · Cited by 58 · see citing works
Yu, H. B., Ma, L., Yang, Y., et al. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030021 · Cited by 58 · see citing works
A systems biology perspective on protein structural dynamics and signal transduction
Rousseau, F., & Schymkowitz, J. W. H. (2005) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2005.01.007 · Cited by 58 · see citing works
Ragona, L., Catalano, M., Luppi, M., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513003200 · Cited by 56 · see citing works
Interactions in Native Binding Sites Cause a Large Change in Protein Dynamics
Ming, D., & Wall, M. E. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.01.097 · Cited by 54 · see citing works
Loop Motions of Triosephosphate Isomerase Observed with Elastic Networks
Kürkçüoğlu, Ö., Jernigan, R. L., & Doruker, P. (2005) · Biochemistry · doi:10.1021/bi0518085 · Cited by 54 · see citing works
Activation Mechanism of a Signaling Protein at Atomic Resolution from Advanced Computations
Ma, L., & Cui, Q. (2007) · Journal of the American Chemical Society · doi:10.1021/ja073059f · Cited by 51 · see citing works
Ensemble‐based signatures of energy propagation in proteins: A new view of an old phenomenon
Liu, T., Whitten, S. T., & Hilser, V. J. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20749 · Cited by 49 · see citing works
Fetler, L., Kantrowitz, E. R., & Vachette, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607641104 · Cited by 43 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Global dynamics of proteins: bridging between structure and function
Bahar, I., Lezon, T. R., Yang, L.-W., & Eyal, E. (2010) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.093008.131258 · Cited by 610 · see citing works
Self-citationAllostery in Its Many Disguises: From Theory to Applications
Wodak, S. J., Paci, E., Dokholyan, N. V., Berezovsky, I. N., Horovitz, A., Li, J., Hilser, V. J., Bahar, I., Karanicolas, J., Stock, G., et al. (2019) · Structure · doi:10.1016/j.str.2019.01.003 · Cited by 404 · see citing works
Self-citationCritical assessment of protein intrinsic disorder prediction
Necci, M., Piovesan, D., Predictors, C., Hoque, M. T., Walsh, I., Iqbal, S., Vendruscolo, M., Sormanni, P., Wang, C., Raimondi, D., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01117-3 · Cited by 343 · see citing works
Chennubhotla, C., Yang, Z., & Bahar, I. (2008) · Molecular BioSystems · doi:10.1039/b717819k · Cited by 102 · see citing works
Self-citationFlechsig, H. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2017.06.043 · Cited by 59 · see citing works
- Authors
- Bahar, I., Chennubhotla, C., & Tobi, D.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Current Opinion in Structural Biology
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 17
- Issue
- 6
- Pages
- 633-640
- ISSN
- 0959-440X (ISSN-L)
- PMC
- PMC2197162
- OpenAlex
- W1991764480
- Cited by
- 306
- References
- 64
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 14 · 2019: 12 · 2018: 13 · 2017: 13 · 2016: 17 · 2015: 15 · 2014: 20 · 2013: 21 · 2012: 27
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r33gm068400-03)
- National Institute of General Medical Sciences (#R33 GM068400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- enzyme dynamics, unbound states, allosteric regulation, conformational sampling, substrate binding, protein conformational dynamics, protein evolution, sequence-structure-function relationships
- MeSH terms
- Allosteric Regulation, Enzymes, Models, Molecular, Protein Conformation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
