Nucleation mechanisms in protein folding
Abstract
Experiment and theory are converging on the importance of nucleation mechanisms in protein folding. These mechanisms do not use classic nuclei, which are well formed elements of structure present in ground states, but they use diffuse, extended regions, which are observed in transition states.
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AlphaFold does not resolve the protein folding problem and does not identify folding pathways.
“AlphaFold does not resolve the decades-long protein folding challenge, nor does it identify the folding pathways.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [54]
Cites
Spin glasses and the statistical mechanics of protein folding.
Bryngelson, J. D., & Wolynes, P. G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7524 · Cited by 1,647 · see citing works
Are there pathways for protein folding?
Levinthal, C. (1968) · Journal de Chimie Physique · doi:10.1051/jcp/1968650044 · Cited by 1,536 · see citing works
Principles of protein folding — A perspective from simple exact models
Dill, K. A., Bromberg, S., Yue, K., Chan, H. S., Fiebig, K. M., Yee, D. P., & Thomas, P. D. (1995) · Protein Science · doi:10.1002/pro.5560040401 · Cited by 1,517 · see citing works
INTERMEDIATES IN THE FOLDING REACTIONS OF SMALL PROTEINS
Kim, P. S., & Baldwin, R. L. (1990) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.59.070190.003215 · Cited by 1,136 · see citing works
Brandts, J. F., Halvorson, H. R., & Brennan, M. (1975) · Biochemistry · doi:10.1021/bi00693a026 · Cited by 1,120 · see citing works
Kim, P. S., & Baldwin, R. L. (1982) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.51.070182.002331 · Cited by 1,036 · see citing works
Šali, A., Shakhnovich, E. I., & Karplus, M. (1994) · Nature · doi:10.1038/369248a0 · Cited by 944 · see citing works
Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition
Jackson, S., & Fersht, A. R. (1991) · Biochemistry · doi:10.1021/bi00107a010 · Cited by 888 · see citing works
Self-citationNucleation, Rapid Folding, and Globular Intrachain Regions in Proteins
Wetlaufer, D. B. (1973) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.70.3.697 · Cited by 836 · see citing works
Theoretical Studies of Protein Folding
Gō, N. (1983) · Annual Review of Biophysics and Bioengineering · doi:10.1146/annurev.bb.12.060183.001151 · Cited by 833 · see citing works
Itzhaki, L. S., Otzen, D. E., & Fersht, A. R. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0616 · Cited by 750 · see citing works
Self-citationIntermediates and barrier crossing in a random energy model (with applications to protein folding)
Bryngelson, J. D., & Wolynes, P. G. (1989) · The Journal of Physical Chemistry · doi:10.1021/j100356a007 · Cited by 746 · see citing works
Šali, A., Shakhnovich, E. I., & Karplus, M. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1110 · Cited by 561 · see citing works
Toward an outline of the topography of a realistic protein-folding funnel.
Onuchic, J. N., Wolynes, P. G., Luthey-Schulten, Z., & Socci, N. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.8.3626 · Cited by 523 · see citing works
Specific Nucleus as the Transition State for Protein Folding: Evidence from the Lattice Model
Abkevich, V., Gutin, A. M., & Shakhnovich, E. I. (1994) · Biochemistry · doi:10.1021/bi00199a029 · Cited by 477 · see citing works
Fersht, A. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.10869 · Cited by 473 · see citing works
Self-citationProtein folding dynamics: The diffusion‐collision model and experimental data
Karplus, M., & Weaver, D. L. (1994) · Protein Science · doi:10.1002/pro.5560030413 · Cited by 447 · see citing works
The barriers in protein folding
Sosnick, T. R., Mayne, L. C., Hiller, R., & Englander, S. W. (1994) · Nature Structural Biology · doi:10.1038/nsb0394-149 · Cited by 433 · see citing works
Kinetics and thermodynamics of folding in model proteins.
Camacho, C. J., & Thirumalai, D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.6369 · Cited by 357 · see citing works
Kinetics of protein folding: Nucleation mechanism, time scales, and pathways
Guo, Z., & Thirumalai, D. (1995) · Biopolymers · doi:10.1002/bip.360360108 · Cited by 336 · see citing works
Conserved residues and the mechanism of protein folding
Shakhnovich, E., Abkevich, V., & Ptitsyn, O. (1996) · Nature · doi:10.1038/379096a0 · Cited by 313 · see citing works
Characterizing transition states in protein folding: an essential step in the puzzle
Fersht, A. R. (1995) · Current Opinion in Structural Biology · doi:10.1016/0959-440x(95)80012-p · Cited by 309 · see citing works
Self-citationProtein folding bottlenecks: A lattice Monte Carlo simulation
Shakhnovich, E. I., Farztdinov, G., Gutin, A. M., & Karplus, M. (1991) · Physical Review Letters · doi:10.1103/physrevlett.67.1665 · Cited by 293 · see citing works
A test of lattice protein folding algorithms.
Yue, K., Fiebig, K. M., Thomas, P. D., Chan, H. S., Shakhnovich, E. I., & Dill, K. A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.1.325 · Cited by 286 · see citing works
Extremely rapid protein folding in the absence of intermediates
Schindler, T. H., Herrler, M., Marahiel, M. A., et al. (1995) · Nature Structural Biology · doi:10.1038/nsb0895-663 · Cited by 283 · see citing works
Theoretical studies of protein folding and unfolding
Karplus, M., & Šali, A. (1995) · Current Opinion in Structural Biology · doi:10.1016/0959-440x(95)80010-x · Cited by 255 · see citing works
Viguera, A. R., Martínez, J. C., Filimonov, V. V., et al. (1994) · Biochemistry · doi:10.1021/bi00174a022 · Cited by 255 · see citing works
Protein folding and stability: the pathway of folding of barnase
Fersht, A. R. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81405-o · Cited by 246 · see citing works
Self-citationFrom Minimal Models to Real Proteins: Time Scales for Protein Folding Kinetics
Thirumalai, D. (1995) · Journal de Physique I · doi:10.1051/jp1:1995209 · Cited by 237 · see citing works
Dissection of the structure and activity of the tyrosyl-tRNA synthetase by site-directed mutagenesis
Fersht, A. R. (1987) · Biochemistry · doi:10.1021/bi00399a001 · Cited by 234 · see citing works
Self-citationCatalysis, binding and enzyme-substrate complementarity
Fersht, A. R. (1974) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1974.0084 · Cited by 233 · see citing works
Self-citationLi, A., & Daggett, V. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0172 · Cited by 229 · see citing works
Structure of the Transition State for Folding of a Protein Derived from Experiment and Simulation
Daggett, V., Li, A., Itzhaki, L. S., et al. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0173 · Cited by 228 · see citing works
Submillisecond folding of monomeric lambda repressor.
Huang, G. S., & Oas, T. G. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.15.6878 · Cited by 219 · see citing works
Different folding transition states may result in the same native structure
Viguera, A. R., Serrano, L. G., & Wilmanns, M. (1996) · Nature Structural & Molecular Biology · doi:10.1038/nsb1096-874 · Cited by 219 · see citing works
Otzen, D. E., Itzhaki, L. S., elMasry, N., et al. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10422 · Cited by 218 · see citing works
Jackson, S., & Fersht, A. R. (1991) · Biochemistry · doi:10.1021/bi00107a011 · Cited by 208 · see citing works
Self-citationAcid and Thermal Denaturation of Barnase Investigated by Molecular Dynamics Simulations
Caflisch, A., & Karplus, M. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0528 · Cited by 177 · see citing works
López-Hernéndez, E., & Serrano, L. (1996) · Folding and Design · doi:10.1016/s1359-0278(96)00011-9 · Cited by 173 · see citing works
Foldons, protein structural modules, and exons.
Panchenko, A. R., Luthey-Schulten, Z. A., & Wolynes, P. G. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.5.2008 · Cited by 170 · see citing works
Kinetics and Thermodynamics of Folding of ade NovoDesigned Four-helix Bundle Protein
Guo, Z., & Thirumalai, D. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0578 · Cited by 169 · see citing works
Skolnick, J., & Koliński, A. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)80070-b · Cited by 167 · see citing works
A simple statistical field theory of heteropolymer collapse with application to protein folding
Bryngelson, J. D., & Wolynes, P. G. (1990) · Biopolymers · doi:10.1002/bip.360300117 · Cited by 162 · see citing works
Alexander, P., Orban, J. P., & Bryan, P. N. (1992) · Biochemistry · doi:10.1021/bi00147a006 · Cited by 161 · see citing works
Is Burst Hydrophobic Collapse Necessary for Protein Folding?
Gutin, A. M., Abkevich, V., & Shakhnovich, E. I. (1995) · Biochemistry · doi:10.1021/bi00009a038 · Cited by 151 · see citing works
Folding of a four-helix bundle: studies of acyl-coenzyme A binding protein
Kragelund, B. B., Robinson, C. V., Knudsen, J., et al. (1995) · Biochemistry · doi:10.1021/bi00021a037 · Cited by 144 · see citing works
Matthews, J. M., & Fersht, A. R. (1995) · Biochemistry · doi:10.1021/bi00020a027 · Cited by 131 · see citing works
Self-citationKuszewski, J. J., Clore, G. M., & Gronenborn, A. M. (1994) · Protein Science · doi:10.1002/pro.5560031106 · Cited by 128 · see citing works
[Stages in the mechanism of self-organization of protein molecules].
Ptitsyn, O. B. (1973) · PubMed · Cited by 118 · see citing works
Folding kinetics of proteins and copolymers
Miller, R. M., Danko, C. A., Fasolka, M. J., Balazs, A. C., Chan, H. S., & Dill, K. A. (1992) · The Journal of Chemical Physics · doi:10.1063/1.462462 · Cited by 113 · see citing works
Fast-folding eriments and the topography of protein folding energy landscapes
Wolynes, P. G., Luthey-Schulten, Z. A., & Onuchic, J. N. (1996) · Chemistry & Biology · doi:10.1016/s1074-5521(96)90090-3 · Cited by 98 · see citing works
Cold Denaturation of Barstar:1H,15N and13C NMR Assignment and Characterisation of Residual Structure
Wong, K., Freund, S. M. V., & Fersht, A. R. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0359 · Cited by 94 · see citing works
Self-citationFavourable native-like helical local interactions can accelerate protein folding
Viguera, A. R., Villegas, S., Avilés, F. X., & Serrano, L. (1997) · Folding and Design · doi:10.1016/s1359-0278(97)00003-5 · Cited by 90 · see citing works
The folding mechanism of larger model proteins: role of native structure.
Dinner, A. R., Šali, A., & Karplus, M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8356 · Cited by 87 · see citing works
Thirumalai, D., & Guo, Z. (1995) · Biopolymers · doi:10.1002/bip.360350114 · Cited by 85 · see citing works
Kinetic and equilibrium intermediates in protein folding
Ptitsyn, O. B. (1994) · Protein Engineering Design and Selection · doi:10.1093/protein/7.5.593 · Cited by 85 · see citing works
Villegas, S., Azuaga, A. I., Catasús, L., et al. (1995) · Biochemistry · doi:10.1021/bi00046a017 · Cited by 80 · see citing works
Initiation sites of protein folding by NMR analysis.
Freund, S. M. V., Wong, K., & Fersht, A. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.10600 · Cited by 74 · see citing works
Self-citationAnalysis of the effect of local interactions on protein stability
Muñoz, V., Cronet, P., López-Hernéndez, E., & Serrano, L. G. (1996) · Folding and Design · doi:10.1016/s1359-0278(96)00029-6 · Cited by 71 · see citing works
Gay, G. D. P., Ruiz‐Sanz, J., Neira, J. L., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.9.3683 · Cited by 68 · see citing works
Search for Nucleation Sites in Smaller Fragments of Chymotrypsin Inhibitor 2
Itzhaki, L. S., Neira, J. L., Ruiz‐Sanz, J., et al. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0617 · Cited by 67 · see citing works
Arcus, V. L., Vuilleumier, S., Freund, S. M. V., et al. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.20.9412 · Cited by 65 · see citing works
How molten is the molten globule?
Ptitsyn, O. B. (1996) · Nature Structural & Molecular Biology · doi:10.1038/nsb0696-488 · Cited by 65 · see citing works
Optimal local propensities for model proteins
Govindarajan, S., & Goldstein, R. A. (1995) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340220411 · Cited by 63 · see citing works
Properties of the Refolding and Unfolding Reactions of Ribonuclease A
Tsong, T. Y., Baldwin, R. L., & Elson, E. L. (1972) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.69.7.1809 · Cited by 47 · see citing works
Domains in folding of model proteins
Abkevich, V., Gutin, A. M., & Shakhnovich, E. I. (1995) · Protein Science · doi:10.1002/pro.5560040615 · Cited by 41 · see citing works
Neira, J. L., Davis, B. J., Ladurner, A. G., et al. (1996) · Folding and Design · doi:10.1016/s1359-0278(96)00031-4 · Cited by 40 · see citing works
Gay, G. D. P., Ruiz‐Sanz, J., Davis, B. J., et al. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10943 · Cited by 38 · see citing works
Protein Folding: An unfolding story
Creighton, T. E. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00070-4 · Cited by 34 · see citing works
Nucleation in protein folding-confusion of structure and process
Wetlaufer, D. B. (1990) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(90)90275-g · Cited by 32 · see citing works
Kippen, A. D., & Fersht, A. R. (1995) · Biochemistry · doi:10.1021/bi00004a042 · Cited by 26 · see citing works
Self-citationP-A4-12 A folding pathway solving Levinthal's paradox
(1996) · Progress in Biophysics and Molecular Biology · doi:10.1016/s0079-6107(97)80173-3 · Cited by 2 · see citing works
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- Authors
- Fersht, A. R.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Fersht, Alan R
- Venue
- Current Opinion in Structural Biology
- Publisher
- Elsevier BV
- Published
- 1997-02
- Volume
- 7
- Issue
- 1
- Pages
- 3-9
- ISSN
- 0959-440X (ISSN-L)
- OpenAlex
- W2079884830
- Cited by
- 545
- References
- 72
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 5 · 2019: 8 · 2018: 7 · 2017: 5 · 2016: 11 · 2015: 11 · 2014: 13 · 2013: 13 · 2012: 19
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- protein folding, nucleation mechanism, folding transition state, folding kinetics, folding free energy landscape
- MeSH terms
- Kinetics, Protein Conformation, Protein Folding
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