Induced fit, conformational selection and independent dynamic segments: an extended view of binding events
Open accessAbstract
Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here, we describe an extended conformational selection model that embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein ('discrete breathers') can govern conformational transitions and allosteric propagation that accompany binding processes and, as such, might be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.
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?
Even if P(Ap) is taken equal to 1 and localization probability is eliminated by collapsing chance to necessity, P(Ac) can still pose huge obstacles to the chance configuration of the quaternary structure of operative biological systems.
“Even if we take P (A p ) equal to 1, and thus assume there are no problematic obstacles involved in generating the building blocks; and also eliminate the localization probability by collapsing chance to necessity (selforganization), P(A c ) can still pose huge obstacles to the chance configuration of the quaternary structure of operative biological systems (Csermely et al., 2010).”
From Using statistical methods to model the fine-tuning of molecular machines and systems (2020) · cites this paper as Csermely et al., 2010
The section on binding in the crowded cellular environment discusses factors that increase and decrease protein encounters, while the section on chaperones describes how they facilitate protein-complex assembly. Neither addresses P(Ac), the assumption that P(Ap) equals 1, or a claimed probability obstacle to forming functional quaternary structures by chance (searched those terms and paraphrases). (LLM, conf=0.75)
Experimental — accuracy not yet measuredPropagation of conformational change at certain locations can cause large-amplitude fluctuations of linked domains.
“The propagation of conformational change at certain locations228–230 can lead to large amplitude fluctuations of the linked domains.231”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [228]
In the induced fit mechanism, ligands bind to the single open protein structure and interaction with a rigid binding partner induces a conformational change.
“In an induced fit scenario, the ligands bind to the single “open” protein structure and the interaction between a protein and a rigid binding partner induces a conformational change in the protein.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [184]
Evidence points to the conformational selection binding mechanism, which allows one to precompute the conformational ensemble of the interacting molecule(s) and dock the separate conformers with limited conformational search.
“In a long-standing debate between the proponents of the “induced-fit” and the “conformational selection” binding mechanisms [21–23], the evidence pointing to the latter allows one to precompute the conformational ensemble of the interacting molecule(s) and dock the separate conformers with limited conformational search [24,25].”
From Challenges in protein docking (2020) · cites this paper as [22]
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
The Energy Landscapes and Motions of Proteins
Frauenfelder, H., Sligar, S. G., & Wolynes, P. G. (1991) · Science · doi:10.1126/science.1749933 · Cited by 3,250 · 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
Macromolecular crowding: obvious but underappreciated
Ellis, R. J. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01938-7 · Cited by 2,309 · 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
Zhou, H., Rivas, G., & Minton, A. P. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.125817 · Cited by 2,130 · see citing works
Intrinsically unstructured proteins
Tompa, P. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02169-2 · Cited by 2,056 · see citing works
The role of dynamic conformational ensembles in biomolecular recognition
Boehr, D. D., Nussinov, R., & Wright, P. E. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.232 · Cited by 2,008 · see citing works
Self-citationEinfluss der Configuration auf die Wirkung der Enzyme
Fischer, E. (1894) · Berichte der deutschen chemischen Gesellschaft · doi:10.1002/cber.18940270364 · Cited by 1,841 · see citing works
Understanding protein non-folding
Uversky, V. N., & Dunker, A. K. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.01.017 · Cited by 1,188 · see citing works
Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution
Lange, O. F., Lakomek, N., Farès, C., Schroeder, G. F., Walter, K. F. A., Becker, S., Meiler, J., Grubmüller, H., Griesinger, C., & de Groot, B. L. (2008) · Science · doi:10.1126/science.1157092 · Cited by 1,044 · see citing works
Dynamical networks in tRNA:protein complexes
Sethi, A., Eargle, J., Black, A. A., & Luthey-Schulten, Z. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810961106 · Cited by 795 · see citing works
Dynamics of Water in Biological Recognition
Pal, S. K., & Zewail, A. H. (2004) · Chemical Reviews · doi:10.1021/cr020689l · Cited by 764 · see citing works
Protein Sectors: Evolutionary Units of Three-Dimensional Structure
Halabi, N. M., Rivoire, O., Leibler, S., & Ranganathan, R. (2009) · Cell · doi:10.1016/j.cell.2009.07.038 · Cited by 697 · see citing works
Crowding Effects on Diffusion in Solutions and Cells
Dix, J. A., & Verkman, A. S. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.125824 · Cited by 669 · see citing works
Folding funnels, binding funnels, and protein function
Tsai, C., Kumar, S., Ma, B., & Nussinov, R. (1999) · Protein Science · doi:10.1110/ps.8.6.1181 · Cited by 648 · see citing works
Self-citationFolding funnels and binding mechanisms
Ma, B., Kumar, S., Tsai, C.-J., & Nussinov, R. (1999) · Protein Engineering, Design and Selection · doi:10.1093/protein/12.9.713 · Cited by 594 · see citing works
Self-citationConformational selection or induced fit: A flux description of reaction mechanism
Hammes, G. G., Chang, Y.-C., & Oas, T. G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907195106 · Cited by 577 · see citing works
The role of structural disorder in the function of RNA and protein chaperones
Tompa, P., & Csermely, P. (2004) · The FASEB Journal · doi:10.1096/fj.04-1584rev · Cited by 555 · see citing works
Self-citationSmock, R. G., & Gierasch, L. M. (2009) · Science · doi:10.1126/science.1169377 · Cited by 508 · see citing works
Allostery: Absence of a change in shape does not imply that allostery is not at play
Tsai, C.-J., del Sol, A., & Nussinov, R. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.02.034 · Cited by 453 · see citing works
Self-citationProtein aggregation in crowded environments
Ellis, R. J., & Minton, A. P. (2006) · Biological Chemistry · doi:10.1515/bc.2006.064 · Cited by 421 · 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
Self-citationVisualization of transient encounter complexes in protein–protein association
Tang, C., Iwahara, J., & Clore, G. M. (2006) · Nature · doi:10.1038/nature05201 · Cited by 406 · see citing works
Stochastic focusing: Fluctuation-enhanced sensitivity of intracellular regulation
Paulsson, J. F., Berg, O. G., & Ehrenberg, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110057697 · Cited by 391 · see citing works
Dynamic activation of an allosteric regulatory protein
Tzeng, S., & Kalodimos, C. G. (2009) · Nature · doi:10.1038/nature08560 · Cited by 378 · see citing works
Edgetic perturbation models of human inherited disorders
Zhong, Q., Simonis, N., Li, Q., Charloteaux, B., Heuze, F., Klitgord, N., Tam, S., Yu, H., Venkatesan, K., Mou, D., et al. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.80 · Cited by 359 · 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
Okazaki, K.-I., & Takada, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802524105 · Cited by 320 · see citing works
Insufficiently dehydrated hydrogen bonds as determinants of protein interactions
Fernández, A., & Scheraga, H. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0136888100 · Cited by 258 · see citing works
Network analysis of protein dynamics
Böde, C., Kovács, I. A., Szalay, M., Palotai, R., Korcsmaros, T. D., & Csermely, P. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.05.021 · Cited by 223 · see citing works
Self-citationLevy, Y., Cho, S. S., Onuchic, J. N., & Wolynes, P. G. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.12.021 · Cited by 213 · see citing works
Ligand-Dependent Equilibrium Fluctuations of Single Calmodulin Molecules
Junker, J. P., Ziegler, F., & Rief, M. (2009) · Science · doi:10.1126/science.1166191 · Cited by 211 · see citing works
Structured disorder and conformational selection
Tsai, C., Ma, B., Sham, Y. Y., Kumar, S., & Nussinov, R. (2001) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.1107 · Cited by 202 · cited 1× · see citing works
“a purely induced fit type binding mechanism is not characteristic even in these cases, because IDPs also have a broad fluctuating conformational ensemble, and conformational selection can take place [49, 50, 51]. The initial binding event of IDPs was proposed to be assisted by a ‘fly-casting’-like search mechanism, wh…”
Self-citationMultiple native states reveal persistent ruggedness of an RNA folding landscape
Solomatin, S. V., Greenfeld, M., Chu, S., & Herschlag, D. (2010) · Nature · doi:10.1038/nature08717 · Cited by 197 · see citing works
Topology Links RNA Secondary Structure with Global Conformation, Dynamics, and Adaptation
Bailor, M. H., Sun, X., & Al‐Hashimi, H. M. (2010) · Science · doi:10.1126/science.1181085 · Cited by 194 · see citing works
Włodarski, T., & Žagrović, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906966106 · Cited by 194 · 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
Schrank, T. P., Bolen, D. W., & Hilser, V. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906510106 · Cited by 171 · see citing works
Selected‐fit versus induced‐fit protein binding: Kinetic differences and mutational analysis
Weikl, T. R., & von Deuster, C. I. E. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22223 · Cited by 169 · see citing works
The origins and evolution of functional modules: lessons from protein complexes
Pereira‐Leal, J. B., Levy, E. D., & Teichmann, S. A. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2005.1807 · Cited by 159 · see citing works
Pechmann, S., Levy, E. D., Tartaglia, G. G., & Vendruscolo, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812414106 · Cited by 159 · see citing works
Boehr, D. D., McElheny, D., Dyson, H. J., & Wright, P. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914163107 · Cited by 142 · see citing works
A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction
Gsponer, J. A., Christodoulou, J. C., Cavalli, A., Bui, J. M., Richter, B., Dobson, C. M., & Vendruscolo, M. (2008) · Structure · doi:10.1016/j.str.2008.02.017 · Cited by 134 · see citing works
Csermely, P. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.09.006 · Cited by 129 · see citing works
Self-citationBashir, Q., Volkov, A. N., Ullmann, G. M., & Ubbink, M. (2009) · Journal of the American Chemical Society · doi:10.1021/ja9064574 · Cited by 125 · see citing works
Transient Non-native Hydrogen Bonds Promote Activation of a Signaling Protein
Gardino, A. K., Villali, J., Kivenson, A., Lei, M., Liu, C. F., Steindel, P. A., Eisenmesser, E. Z., Labeikovsky, W., Wolf‐Watz, M., Clarkson, M. W., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.022 · Cited by 107 · see citing works
Reichheld, S. E., Yu, Z., & Davidson, A. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0911566106 · 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
Toward a quantitative theory of intrinsically disordered proteins and their function
Liu, J., Faeder, J. R., & Camacho, C. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907710106 · Cited by 102 · see citing works
del Sol, A., Araúzo-Bravo, M. J., Amoros, D., & Nussinov, R. (2007) · Genome biology · doi:10.1186/gb-2007-8-5-r92 · Cited by 92 · see citing works
Self-citationCapillarity theory for the fly-casting mechanism
Trizac, E., Levy, Y., & Wolynes, P. G. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914727107 · Cited by 82 · see citing works
Use of Game-Theoretical Methods in Biochemistry and Biophysics
Schuster, S., Kreft, J., Schroeter, A., & Pfeiffer, T. (2008) · Journal of Biological Physics · doi:10.1007/s10867-008-9101-4 · Cited by 76 · see citing works
Confinement effects on the kinetics and thermodynamics of protein dimerization
Wang, W., Xu, W., Levy, Y., Trizac, E., & Wolynes, P. G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809649106 · Cited by 76 · see citing works
Discrete breathers in protein structures
Piazza, F., & Sanejouand, Y.-H. (2008) · Physical Biology · doi:10.1088/1478-3975/5/2/026001 · Cited by 75 · see citing works
Haliloǧlu, T., Keskin, Ö., Ma, B., & Nussinov, R. (2005) · Biophysical Journal · doi:10.1529/biophysj.104.051342 · Cited by 70 · see citing works
Self-citationKovács, I. A., Szalay, M., & Csermely, P. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.03.056 · Cited by 66 · see citing works
Self-citationA finite element framework for computation of protein normal modes and mechanical response
Bathe, M. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21708 · Cited by 64 · see citing works
Antal, M., Böde, C., & Csermely, P. (2009) · Current Protein and Peptide Science · doi:10.2174/138920309787847617 · Cited by 62 · see citing works
Self-citationLong-range energy transfer in proteins
Piazza, F., & Sanejouand, Y.-H. (2009) · Physical Biology · doi:10.1088/1478-3975/6/4/046014 · Cited by 58 · see citing works
Decomposition of Gene Expression State Space Trajectories
Mar, J. C., & Quackenbush, J. F. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000626 · Cited by 40 · see citing works
Gorfe, A. A., Baron, R., & McCammon, J. A. (2008) · Biophysical Journal · doi:10.1529/biophysj.108.136481 · Cited by 34 · see citing works
Materese, C. K., Goldmon, C. C., & Papoian, G. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801850105 · Cited by 33 · see citing works
Desolvation shell of hydrogen bonds in folded proteins, protein complexes and folding pathways
Fernández, A. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03204-0 · Cited by 19 · see citing works
The Goldbeter-Koshland Switch in the First-Order Region and Its Response to Dynamic Disorder
Xing, J., & Chen, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002140 · Cited by 19 · see citing works
Games network and application to PAs system
Chettaoui, C., Delaplace, F., Manceny, M., & Malo, M. (2006) · Biosystems · doi:10.1016/j.biosystems.2006.09.006 · Cited by 17 · see citing works
Wu, Z., Elgart, V., Qian, H., & Xing, J. (2009) · The Journal of Physical Chemistry B · doi:10.1021/jp903548d · Cited by 12 · see citing works
Závodszky, P., Biszku, E., Lv, A., & Szabolcsi, G. (1972) · PubMed · Cited by 4 · see citing works
Finite Element Framework for Mechanics and Dynamics of Supramolecular Protein Assemblies
Kim, D., Sedeh, R. S., Nguyen, C.-T., & Bathe, M. (2010) · ASME Global Congress on NanoEngineering for Medicine and Biology (NEMB) · doi:10.1115/nemb2010-13312 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
Du, X., Li, Y., Xia, Y.-L., Ai, S.-M., Liang, J., Sang, P., Ji, X., & Liu, S.-Q. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020144 · Cited by 1,669 · see citing works
Vital nodes identification in complex networks
Lü, L., Chen, D., Ren, X.-L., Zhang, Q.-M., Zhang, Y., & Zhou, T. (2016) · Physics Reports · doi:10.1016/j.physrep.2016.06.007 · Cited by 1,287 · see citing works
Molecular dynamics simulations: advances and applications
Gelpí, J. L., Hospital, A., Goñi, R., & Orozco, M. (2015) · Advances and Applications in Bioinformatics and Chemistry · doi:10.2147/aabc.s70333 · Cited by 951 · see citing works
Structure and dynamics of molecular networks: A novel paradigm of drug discovery
Csermely, P., Korcsmáros, T., Kiss, H., London, G., & Nussinov, R. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.016 · Cited by 889 · see citing works
Self-citationAllostery in Disease and in Drug Discovery
Nussinov, R., & Tsai, C. (2013) · Cell · doi:10.1016/j.cell.2013.03.034 · Cited by 764 · see citing works
Self-citationSalmaso, V., & Moro, S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00923 · Cited by 675 · see citing works
An introduction to NMR-based approaches for measuring protein dynamics
Kleckner, I. R., & Foster, M. P. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.10.012 · Cited by 565 · see citing works
On the binding affinity of macromolecular interactions: daring to ask why proteins interact
Kastritis, P. L., & Bonvin, A. M. J. J. (2012) · Journal of The Royal Society Interface · doi:10.1098/rsif.2012.0835 · Cited by 519 · see citing works
Ensemble Docking in Drug Discovery.
Amaro, R., Baudry, J., Chodera, J., Demir, Ö., McCammon, J., Miao, Y.-L., & Smith, J. C. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2018.02.038 · Cited by 435 · see citing works
Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436 · see citing works
Self-citationThe Role of Protein Loops and Linkers in Conformational Dynamics and Allostery
Papaleo, E., Saladino, G., Lambrughi, M., Lindorff‐Larsen, K., Gervasio, F. L., & Nussinov, R. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00623 · Cited by 426 · see citing works
Self-citationCurrin, A., Swainston, N., Day, P. J., & Kell, D. B. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00351a · Cited by 383 · see citing works
Chemical control of structure and guest uptake by a conformationally mobile porous material
Katsoulidis, A. P., Antypov, D., Whitehead, G. F. S., Carrington, E. J., Adams, D. J., Berry, N. G., Darling, G. R., Dyer, M. S., & Rosseinsky, M. J. (2019) · Nature · doi:10.1038/s41586-018-0820-9 · Cited by 329 · see citing works
Plasticity of an Ultrafast Interaction between Nucleoporins and Nuclear Transport Receptors
Milles, S., Mercadante, D., Aramburu, I. V., Jensen, M. R., Banterle, N., Koehler, C., Tyagi, S., Clarke, J., Shammas, S. L., Blackledge, M. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.047 · Cited by 304 · see citing works
Jensen, M. R., Zweckstetter, M., Huang, J., & Blackledge, M. J. (2014) · Chemical Reviews · doi:10.1021/cr400688u · Cited by 298 · see citing works
Nonspecific Binding—Fundamental Concepts and Consequences for Biosensing Applications
Frutiger, A., Tanno, A., Hwu, S., Tiefenauer, R. F., Vörös, J., & Nakatsuka, N. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00044 · Cited by 282 · see citing works
Góra, A., Brezovský, J., & Damborský, J. (2013) · Chemical Reviews · doi:10.1021/cr300384w · Cited by 280 · see citing works
Bowman, G. R., & Geissler, P. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209309109 · Cited by 279 · see citing works
Controlling Allosteric Networks in Proteins
Dokholyan, N. V. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00544 · Cited by 260 · see citing works
Zhuravleva, A., Clerico, E. M., & Gierasch, L. (2012) · Cell · doi:10.1016/j.cell.2012.11.002 · Cited by 253 · see citing works
A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein
Silva, D., Bowman, G. R., Sosa‐Peinado, A., & Huang, X. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002054 · Cited by 227 · see citing works
Biophysics of protein evolution and evolutionary protein biophysics
Sikosek, T., & Chan, H. S. (2014) · Journal of The Royal Society Interface · doi:10.1098/rsif.2014.0419 · Cited by 220 · see citing works
Dynamic Allostery: Linkers Are Not Merely Flexible
Ma, B., Tsai, C.-J., Haliloğlu, T., & Nussinov, R. (2011) · Structure · doi:10.1016/j.str.2011.06.002 · Cited by 222 · see citing works
Self-citationNetworkView: 3D display and analysis of protein·RNA interaction networks
Eargle, J., & Luthey-Schulten, Z. A. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts546 · Cited by 221 · see citing works
Understanding Cryptic Pocket Formation in Protein Targets by Enhanced Sampling Simulations
Oleinikovas, V., Saladino, G., Cossins, B. P., & Gervasio, F. L. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b05425 · Cited by 220 · see citing works
Abyzov, A., Blackledge, M., & Zweckstetter, M. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00774 · Cited by 215 · see citing works
Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics
Maximova, T., Moffatt, R., Ma, B., Nussinov, R., & Shehu, A. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004619 · Cited by 211 · see citing works
Self-citationAllostery without a conformational change? Revisiting the paradigm
Nussinov, R., & Tsai, C.-J. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2014.11.005 · Cited by 202 · see citing works
Self-citationMapping allosteric communications within individual proteins
Wang, J., Jain, A., McDonald, L. R., Gambogi, C., Lee, A. L., & Dokholyan, N. V. (2020) · Nature Communications · doi:10.1038/s41467-020-17618-2 · Cited by 201 · see citing works
Bauer, M. R., Ibrahim, T. M., Vogel, S. M., & Boeckler, F. M. (2013) · Journal of Chemical Information and Modeling · doi:10.1021/ci400115b · Cited by 200 · see citing works
A Unified Conformational Selection and Induced Fit Approach to Protein-Peptide Docking
Trellet, M. E., Melquiond, A. S. J., & Bonvin, A. M. J. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058769 · Cited by 200 · see citing works
Structural Characterization of Intrinsically Disordered Proteins by NMR Spectroscopy
Kosol, S., Contreras-Martos, S., Cedeño, C., & Tompa, P. (2013) · Molecules · doi:10.3390/molecules180910802 · Cited by 199 · see citing works
AlphaFold, Artificial Intelligence (AI), and Allostery
Nussinov, R., Zhang, M., Liu, Y., & Jang, H. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c04346 · Cited by 190 · see citing works
Self-citationComputational prediction of protein–protein binding affinities
Siebenmorgen, T., & Zacharias, M. (2020) · WIREs Computational Molecular Science · doi:10.1002/wcms.1448 · Cited by 184 · see citing works
“11,13 Within this ensemble, there are structures close to the bound and unbound forms and the process of binding to partner molecules shifts the ensemble toward the bound form.”
BackgroundBinding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment
Mollica, L., Bessa, L. M., Hanoulle, X., Jensen, M. R., Blackledge, M. J., & Schneider, R. C. (2016) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2016.00052 · Cited by 176 · see citing works
Expanding the proteome: disordered and alternatively folded proteins
Dyson, H. J. (2011) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583511000060 · Cited by 173 · see citing works
The Underappreciated Role of Allostery in the Cellular Network
Nussinov, R., Tsai, C., & Ma, B. (2013) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-083012-130257 · Cited by 174 · see citing works
Self-citationOn the role of electrostatics in protein–protein interactions
Zhang, Z., Witham, S., & Alexov, E. G. (2011) · Physical Biology · doi:10.1088/1478-3975/8/3/035001 · Cited by 169 · see citing works
Protein dynamics and function from solution state NMR spectroscopy
Kovermann, M., Rogne, P., & Wolf‐Watz, M. (2016) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583516000019 · Cited by 172 · see citing works
Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics
Iversen, L., Tu, H.-L., Lin, W.-C., Christensen, S. M., Abel, S. M., Iwig, J., Wu, H.-J., Gureasko, J., Rhodes, C., Petit, R. S., et al. (2014) · Science · doi:10.1126/science.1250373 · Cited by 154 · see citing works
Helical Propensity in an Intrinsically Disordered Protein Accelerates Ligand Binding
Iešmantavičius, V., Dogan, J., Jemth, P., Teilum, K., & Kjærgaard, M. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307712 · Cited by 162 · see citing works
Li, W., Wolynes, P. G., & Takada, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018983108 · Cited by 159 · see citing works
The Hydrophobic Effects: Our Current Understanding
Sun, Q. (2022) · Molecules · doi:10.3390/molecules27207009 · Cited by 167 · see citing works
Protein conformational dynamics dictate the binding affinity for a ligand
Seo, M., Park, J., Kim, E., Hohng, S., & Kim, H. (2014) · Nature Communications · doi:10.1038/ncomms4724 · Cited by 156 · see citing works
Passive immunotherapies targeting Aβ and tau in Alzheimer's disease
Plotkin, S. S., & Cashman, N. R. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105010 · Cited by 156 · see citing works
Principles of Allosteric Interactions in Cell Signaling
Nussinov, R., Tsai, C.-J., & Liu, J. (2014) · Journal of the American Chemical Society · doi:10.1021/ja510028c · Cited by 154 · see citing works
Self-citationExploring the role of receptor flexibility in structure-based drug discovery
Feixas, F., Lindert, S., Sinko, W., & McCammon, J. A. (2014) · Biophysical Chemistry · doi:10.1016/j.bpc.2013.10.007 · Cited by 156 · see citing works
Rogers, J. M., Oleinikovas, V., Shammas, S. L., Wong, C. T., Sancho, D. D., Baker, C. M., & Clarke, J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409122111 · Cited by 150 · see citing works
Cavalli, A., Spitaleri, A., Saladino, G., & Gervasio, F. L. (2014) · Accounts of Chemical Research · doi:10.1021/ar500356n · Cited by 149 · see citing works
Camacho‐Zarco, A. R., Schnapka, V., Guseva, S., Abyzov, A., Adamski, W., Milles, S., Jensen, M. R., Žı́dek, L., Salvi, N., & Blackledge, M. J. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c01023 · Cited by 148 · see citing works
Harnessing Allostery: A Novel Approach to Drug Discovery
Lu, S., Li, S., & Zhang, J. (2014) · Medicinal Research Reviews · doi:10.1002/med.21317 · Cited by 146 · see citing works
Schneider, R. C., Maurin, D., Communie, G., Kragelj, J., Hansen, D. F., Ruigrok, R. W. H., Jensen, M. R., & Blackledge, M. J. (2014) · Journal of the American Chemical Society · doi:10.1021/ja511066q · Cited by 143 · see citing works
Allo-network drugs: harnessing allostery in cellular networks
Nussinov, R., Tsai, C., & Csermely, P. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.08.004 · Cited by 143 · see citing works
Self-citationA Double-Walled Knotted Cage for Guest-Adaptive Molecular Recognition
Tamura, Y., Takezawa, H., & Fujita, M. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c00459 · Cited by 138 · see citing works
Ni, D., Wei, J., He, X., Rehman, A. U., Li, X., Qiu, Y., Pu, J., Lu, S., & Zhang, J. (2020) · Chemical Science · doi:10.1039/d0sc05131d · Cited by 137 · see citing works
Conformational selection in protein binding and function
Weikl, T., & Paul, F. (2014) · Protein Science · doi:10.1002/pro.2539 · Cited by 141 · see citing works
The role of protein conformational fluctuations in allostery, function, and evolution
Wrabl, J. O., Gu, J., Liu, T., Schrank, T. P., Whitten, S. T., & Hilser, V. J. (2011) · Biophysical Chemistry · doi:10.1016/j.bpc.2011.05.020 · Cited by 134 · see citing works
Understanding the challenges of protein flexibility in drug design.
Antunes, D. A., Devaurs, D., & Kavraki, L. E. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1094458 · Cited by 131 · see citing works
Disordered Proteinaceous Machines
Fuxreiter, M., Tóth-Petróczy, Á., Kraut, D. A., Matouschek, A. T., Lim, R. Y. H., Xue, B., Kurgan, L., & Uversky, V. N. (2014) · Chemical Reviews · doi:10.1021/cr4007329 · Cited by 133 · see citing works
Conformational dynamics in substrate-binding domains influences transport in the ABC importer GlnPQ
Gouridis, G., Schuurman‐Wolters, G. K., Ploetz, E., Husada, F., Vietrov, R., de Boer, M., Cordes, T., & Poolman, B. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2929 · Cited by 132 · see citing works
Multiple conformational selection and induced fit events take place in allosteric propagation
Nussinov, R., Ma, B., & Tsai, C. (2013) · Biophysical Chemistry · doi:10.1016/j.bpc.2013.10.002 · Cited by 130 · see citing works
Self-citationNussinov, R., Jang, H., Tsai, C., & Cheng, F. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006658 · Cited by 129 · see citing works
Self-citationSequestration of a β‐Hairpin for Control of α‐Synuclein Aggregation
Mirecka, E. A., Shaykhalishahi, H., Gauhar, A., Akgül, Ş., Lecher, J., Willbold, D., Stoldt, M., & Hoyer, W. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201309001 · Cited by 127 · see citing works
A single-molecule dissection of ligand binding to a protein with intrinsic dynamics
Kim, E., Lee, S.-H., Jeon, A., Choi, J. M., Lee, H., Hohng, S., & Kim, H. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1213 · Cited by 120 · see citing works
Abyzov, A., Salvi, N., Schneider, R., Maurin, D., Ruigrok, R. W. H., Jensen, M. R., & Blackledge, M. J. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b02424 · Cited by 117 · see citing works
Combined strategies in structure-based virtual screening
Wang, Z., Sun, H., Shen, C., Hu, X., Gao, J., Li, D., Cao, D., & Hou, T. (2020) · Physical Chemistry Chemical Physics · doi:10.1039/c9cp06303j · Cited by 116 · see citing works
Rogers, J. M., Wong, C. T., & Clarke, J. (2014) · Journal of the American Chemical Society · doi:10.1021/ja4125065 · Cited by 113 · see citing works
Knott, M., & Best, R. B. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002605 · Cited by 113 · see citing works
The Design of Covalent Allosteric Drugs
Nussinov, R., & Tsai, C.-J. (2015) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124401 · Cited by 112 · see citing works
Self-citationWang, Y., Chu, X., Longhi, S., Roche, P., Han, W., Wang, E., & Wang, J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308381110 · Cited by 110 · see citing works
Predictive energy landscapes for protein–protein association
Zheng, W., Schafer, N. P., Davtyan, A., Papoian, G. A., & Wolynes, P. G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216215109 · Cited by 110 · see citing works
Application of NMR to studies of intrinsically disordered proteins
Gibbs, E. B., Cook, E. C., & Showalter, S. A. (2017) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2017.05.008 · Cited by 108 · see citing works
Disease mutations in disordered regions—exception to the rule?
Vacic, V., & Iakoucheva, L. M. (2011) · Molecular BioSystems · doi:10.1039/c1mb05251a · Cited by 104 · see citing works
Fabre, B., Ramos, A., & de Pascual‐Teresa, B. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500505f · Cited by 106 · see citing works
Mechanical modulation of catalytic power on F1-ATPase
Watanabe, R., Okuno, D., Sakakihara, S., Shimabukuro, K., Iino, R., Yoshida, M., & Noji, H. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.715 · Cited by 105 · see citing works
Understanding intramembrane proteolysis: from protein dynamics to reaction kinetics
Langosch, D., Scharnagl, C., Steiner, H., & Lemberg, M. K. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.04.001 · Cited by 104 · see citing works
Metal binding sites in amyloid oligomers: Complexes and mechanisms
Miller, Y., Ma, B., & Nussinov, R. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2011.12.022 · Cited by 103 · see citing works
Self-citationASD v2.0: updated content and novel features focusing on allosteric regulation
Huang, Z., Mou, L., Shen, Q., Lu, S., Li, C., Liu, X., Wang, G., Li, S., Geng, L., Liu, Y., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1247 · Cited by 102 · see citing works
Computational Approaches to Predict Protein–Protein Interactions in Crowded Cellular Environments
Grassmann, G., Miotto, M., Desantis, F., Rienzo, L. D., Tartaglia, G. G., Pastore, A., Ruocco, G., Monti, M. M., & Milanetti, E. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00550 · Cited by 106 · see citing works
SPACER: server for predicting allosteric communication and effects of regulation
Goncearenco, A., Mitternacht, S., Yong, T., Eisenhaber, B., Eisenhaber, F., & Berezovsky, I. N. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt460 · Cited by 102 · see citing works
Advances in all atom sampling methods for modeling protein–ligand binding affinities
Gallicchio, E., & Levy, R. M. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.01.010 · Cited by 101 · see citing works
Bucher, D., Grant, B. J., & McCammon, J. A. (2011) · Biochemistry · doi:10.1021/bi201481a · Cited by 100 · see citing works
Bremer, A., Wolff, M., Thalhammer, A., & Hincha, D. K. (2017) · FEBS Journal · doi:10.1111/febs.14023 · Cited by 100 · see citing works
Fernández‐Quintero, M. L., Loeffler, J. R., Kraml, J., Kahler, U., Kamenik, A. S., & Liedl, K. R. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03065 · Cited by 96 · see citing works
Conformational selection in protein binding and function
Weikl, T., & Paul, F. (2014) · Max Planck Digital Library · Cited by 91 · see citing works
Blacklock, K. M., & Verkhivker, G. M. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003679 · Cited by 90 · see citing works
Dogan, J., Schmidt, T., Mu, X. N., Engström, Å., & Jemth, P. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.399436 · Cited by 87 · see citing works
Bren, U., & Oostenbrink, C. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci300118x · Cited by 86 · see citing works
Connecting the Kinetics and Energy Landscape of tRNA Translocation on the Ribosome
Whitford, P. C., Blanchard, S. C., Cate, J. H. D., & Sanbonmatsu, K. Y. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003003 · Cited by 86 · see citing works
Recent advances in atomic molecular dynamics simulation of intrinsically disordered proteins
Wang, W. (2020) · Physical Chemistry Chemical Physics · doi:10.1039/d0cp05818a · Cited by 83 · see citing works
Using azobenzene photocontrol to set proteins in motion
Božović, O., Janković, B. G., & Hamm, P. M. (2022) · Zurich Open Repository and Archive (University of Zurich) · doi:10.1038/s41570-021-00338-6 · Cited by 85 · see citing works
Zhang, W., Ganguly, D., & Chen, J. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002353 · Cited by 84 · see citing works
Building a virtual ligand screening pipeline using free software: a survey
Glaab, E. (2015) · Briefings in Bioinformatics · doi:10.1093/bib/bbv037 · Cited by 84 · see citing works
NMR line shapes and multi-state binding equilibria
Kovrigin, E. L. (2012) · Journal of Biomolecular NMR · doi:10.1007/s10858-012-9636-3 · Cited by 83 · see citing works
Greives, N., & Zhou, H.-X. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407545111 · Cited by 82 · see citing works
Wang, X., Liu, D., Shen, L., Li, F., Li, Y., Yang, L., Xu, T., Tao, H., Yao, D., Wu, L., et al. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c06847 · Cited by 82 · see citing works
Selective Molecular Recognition in Amyloid Growth and Transmission and Cross-Species Barriers
Ma, B., & Nussinov, R. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.11.023 · Cited by 81 · see citing works
Self-citationxPyder: A PyMOL Plugin To Analyze Coupled Residues and Their Networks in Protein Structures.
Pasi, M., Tiberti, M., Arrigoni, A., & Papaleo, E. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci300213c · Cited by 80 · see citing works
Baker, B. M., Scott, D. R., Blevins, S. J., & Hawse, W. F. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01165.x · Cited by 80 · see citing works
Gaudreault, F., Chartier, M., & Najmanovich, R. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts395 · Cited by 80 · see citing works
- Authors
- Csermely, P., Palotai, R., & Nussinov, R.
- Affiliations
- Semmelweis University (HU)
- Tel Aviv University (IL)
- ORCID
- Nussinov, Ruth
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 35
- Issue
- 10
- Pages
- 539-546
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC3018770
- OpenAlex
- W2096929343
- Cited by
- 821
- References
- 69
- Citations by year
- 2026: 40 · 2025: 47 · 2024: 33 · 2023: 23 · 2022: 43 · 2021: 36 · 2020: 56 · 2019: 48 · 2018: 44 · 2017: 49 · 2016: 60 · 2015: 58 · 2014: 75 · 2013: 73 · 2012: 72
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Funders
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (HHSN261200800001E), Z01BC010441)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- induced fit, conformational selection, protein-protein binding, protein dynamics, discrete breathers, conformational change, protein aggregation, cellular crowding
- MeSH terms
- Animals, Humans, Protein Binding, Protein Conformation, Proteins, Signal Transduction, Protein Folding
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
