Folding kinetics and unfolded state dynamics of the GB1 hairpin from molecular simulation
Abstract
The C-terminal β-hairpin of protein G is a 16-residue peptide that folds in a two-state fashion akin to many larger proteins. However, with an experimental folding time of ∼6 μs, it remains a challenging system for all-atom, explicitly solvated, molecular dynamics simulations. Here, we use a large simulation data set (0.7 ms total) of the hairpin at 300 and 350 K to interpret its folding via a master equation approach. We find a separation of over an order of magnitude between the longest and second longest relaxation times, with the slowest relaxation corresponding to folding. However, in spite of this apparent two-state dynamics, the folding rate determined based on a first-passage time analysis depends on the initial conditions chosen, with a nonexponential distribution of first passage times being obtained in some cases. Using the master equation model, we are now able to account quantitatively for the observed distribution of first passage times. The deviation from the expected exponential distribution for a two-state system arises from slow dynamics in the unfolded state, associated with formation and melting of helical structures. Our results help to reconcile recent findings of slow dynamics in unfolded proteins with observed two-state folding kinetics. At the same time, they indicate that care is required in estimating folding kinetics from many short folding simulations. Last, we are able to use the master equation model to obtain details of the folding mechanism and folding transition state, which appear consistent with the "zipper" mechanism inferred from the experiment.
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The MSM approach has led to the construction of extremely detailed statistical models of folding mechanism and unfolded state dynamics for some small peptides and proteins.
“By contrast, the MSM approach has led to the construction of extremely detailed statistical models of folding mechanism and unfolded state dynamics for some small peptides and proteins (e.g. [44, 45]).”
From Markov state models of biomolecular conformational dynamics (2014) · cites this paper as [44]
Cites
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,335 · see citing works
Bootstrap methods: another look at the jackknife
Efron, B. (1979) · The Annals of Statistics · doi:10.1214/aos/1176344552 · Cited by 17,602 · see citing works
Comparison of multiple Amber force fields and development of improved protein backbone parameters
Horn̆ák, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A. E., & Simmerling, C. L. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21123 · Cited by 6,903 · see citing works
Depth-First Search and Linear Graph Algorithms
Tarjan, R. E. (1972) · SIAM Journal on Computing · doi:10.1137/0201010 · Cited by 6,171 · see citing works
Improved side-chain torsion potentials for the Amber ff99SB protein force field
Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J., Dror, R., & Shaw, D. (2010) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.22711 · Cited by 6,037 · see citing works
Kaminski, G. A., Friesner, R. A., Tirado‐Rives, J., & Jorgensen, W. L. (2001) · The Journal of Physical Chemistry B · doi:10.1021/jp003919d · Cited by 4,077 · see citing works
How fast-folding proteins fold
Lindorff-Larsen, K., Piana, S., Dror, R. O., & Shaw, D. E. (2011) · Science · doi:10.1126/science.1208351 · Cited by 1,980 · see citing works
Markov models of molecular kinetics: Generation and validation
Prinz, J.-H., Wu, H., Sarich, M., Keller, B., Senne, M., Held, M., Chodera, J. D., Schütte, C., & Noé, F. (2011) · The Journal of Chemical Physics · doi:10.1063/1.3565032 · Cited by 1,275 · see citing works
Folding dynamics and mechanism of β-hairpin formation
Muñoz, V., Thompson, P. A., Hofrichter, J., & Eaton, W. A. (1997) · Nature · doi:10.1038/36626 · Cited by 929 · see citing works
Optimized Molecular Dynamics Force Fields Applied to the Helix−Coil Transition of Polypeptides
Best, R. B., & Hummer, G. (2009) · The Journal of Physical Chemistry B · doi:10.1021/jp901540t · Cited by 836 · see citing works
Self-citationThe protein folding ‘speed limit’
Kubelka, J., Hofrichter, J., & Eaton, W. A. (2004) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2004.01.013 · Cited by 832 · see citing works
Constructing the equilibrium ensemble of folding pathways from short off-equilibrium simulations
Noé, F., Schütte, C., Vanden-Eijnden, E., Reich, L., & Weikl, T. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905466106 · Cited by 820 · see citing works
A Novel, Highly Stable Fold of the Immunoglobulin Binding Domain of Streptococcal Protein G
Gronenborn, A. M., Filpula, D. R., Essig, N. Z., Achari, A., Whitlow, M. D., Wingfield, P. T., & Clore, G. M. (1991) · Science · doi:10.1126/science.1871600 · Cited by 816 · see citing works
Absolute comparison of simulated and experimental protein-folding dynamics
Snow, C. D., Nguyen, H., Pande, V. S., & Gruebele, M. (2002) · Nature · doi:10.1038/nature01160 · Cited by 701 · see citing works
A simple model for calculating the kinetics of protein folding from three-dimensional structures
Muñoz, V., & Eaton, W. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11311 · Cited by 636 · see citing works
Chodera, J., Singhal, N., Pande, V., Dill, K., & Swope, W. (2007) · Journal of Chemical Physics · doi:10.1063/1.2714538 · Cited by 613 · see citing works
Screen Savers of the World Unite!
Shirts, M., & Pande, V. (2000) · Science · doi:10.1126/science.290.5498.1903 · Cited by 550 · see citing works
A short linear peptide that folds into a native stable β-hairpin in aqueous solution
Blanco, F. J., Rivas, G., & Serrano, L. (1994) · Nature Structural & Molecular Biology · doi:10.1038/nsb0994-584 · Cited by 534 · see citing works
Free-Energy Landscape for β Hairpin Folding from Combined Parallel Tempering and Metadynamics
Bussi, G., Gervasio, F. L., Laio, A., & Parrinello, M. (2006) · Journal of the American Chemical Society · doi:10.1021/ja062463w · Cited by 507 · see citing works
Fast Kinetics and Mechanisms in Protein Folding
Eaton, W. A., Muñoz, V., Hagen, S. J., Jas, G. S., Lapidus, L. J., Henry, E. R., & Hofrichter, J. (2000) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.29.1.327 · Cited by 489 · see citing works
The free energy landscape for β hairpin folding in explicit water
Zhou, R., Berne, B. J., & Germain, R. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201543998 · Cited by 483 · see citing works
Coarse master equations for peptide folding dynamics
Buchete, N.-V., & Hummer, G. (2008) · The Journal of Physical Chemistry B · doi:10.1021/jp0761665 · Cited by 477 · see citing works
Describing Protein Folding Kinetics by Molecular Dynamics Simulations. 1. Theory
Swope, W., Pitera, J., & Suits, F. (2004) · The Journal of Physical Chemistry B · doi:10.1021/jp037421y · Cited by 450 · see citing works
Are Protein Force Fields Getting Better? A Systematic Benchmark on 524 Diverse NMR Measurements
Beauchamp, K., Lin, Y.-S., Das, R., & Pande, V. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct2007814 · Cited by 394 · see citing works
Noé, F., Horenko, I., Schütte, C., & Smith, J. C. (2007) · Journal of Chemical Physics · doi:10.1063/1.2714539 · Cited by 377 · see citing works
MSMBuilder2: Modeling Conformational Dynamics on the Picosecond to Millisecond Scale
Beauchamp, K. A., Bowman, G. R., Lane, T. J., Maibaum, L., Haque, I. S., & Pande, V. S. (2011) · Journal of Chemical Theory and Computation · doi:10.1021/ct200463m · Cited by 372 · see citing works
Hidden complexity of free energy surfaces for peptide (protein) folding.
Krivov, S., & Karplus, M. (2004) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0406234101 · Cited by 336 · see citing works
A statistical mechanical model for β-hairpin kinetics
Muñoz, V., Henry, E. R., Hofrichter, J., & Eaton, W. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.5872 · Cited by 334 · see citing works
Identification of almost invariant aggregates in reversible nearly uncoupled Markov chains
Deuflhard, P., Huisinga, W., Fischer, A., & Schütte, C. (2000) · Linear Algebra and its Applications · doi:10.1016/s0024-3795(00)00095-1 · Cited by 319 · see citing works
Žagrović, B., Sorin, E. J., & Pande, V. S. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5033 · Cited by 269 · see citing works
Mechanisms and kinetics of β-hairpin formation
Klimov, D. K., & Thirumalai, D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.6.2544 · Cited by 244 · see citing works
How Well Can Simulation Predict Protein Folding Kinetics and Thermodynamics?
Snow, C. D., Sorin, E. J., Rhee, Y. M., & Pande, V. S. (2004) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.34.040204.144447 · Cited by 236 · see citing works
Markov state models based on milestoning
Schütte, C., Noé, F., Lu, J., Sarich, M., & Vanden-Eijnden, E. (2011) · The Journal of Chemical Physics · doi:10.1063/1.3590108 · Cited by 228 · see citing works
Transition-path sampling of β-hairpin folding
Bolhuis, P. G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1534924100 · Cited by 216 · see citing works
Protein folded states are kinetic hubs
Bowman, G., & Pande, V. (2010) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1003962107 · Cited by 216 · see citing works
Scrutinizing Molecular Mechanics Force Fields on the Submicrosecond Timescale with NMR Data
Lange, O. F., van der Spoel, D., & de Groot, B. L. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.04.062 · Cited by 199 · see citing works
Force Field Bias in Protein Folding Simulations
Freddolino, L., Park, S., Roux, B., & Schulten, K. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.02.033 · Cited by 197 · see citing works
Understanding the key factors that control the rate of β-hairpin folding
Du, D., Zhu, Y., Huang, C., & Gai, F. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405904101 · Cited by 195 · see citing works
Reactive flux and folding pathways in network models of coarse-grained protein dynamics
Berezhkovskii, A. M., Hummer, G., & Szabó, A. (2009) · The Journal of Chemical Physics · doi:10.1063/1.3139063 · Cited by 170 · see citing works
Thermodynamics of a β-hairpin structure: evidence for cooperative formation of folding nucleus
Honda, S., Kobayashi, N., & Munekata, E. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3346 · Cited by 162 · see citing works
Simple few-state models reveal hidden complexity in protein folding
Beauchamp, K. A., McGibbon, R., Lin, Y.-S., & Pande, V. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201810109 · Cited by 161 · see citing works
Voelz, V. A., Jäger, M., Yao, S., Chen, Y., Zhu, L., Waldauer, S. A., Bowman, G. R., Friedrichs, M., Bakajin, O., Lapidus, L. J., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja302528z · Cited by 140 · see citing works
Atomistic molecular simulations of protein folding
Best, R. B. (2012) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.12.001 · Cited by 139 · see citing works
Self-citationProtein folding pathways from replica exchange simulations and a kinetic network model
Andrec, M., Felts, A. K., Gallicchio, E., & Levy, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408970102 · Cited by 137 · see citing works
Folding of the GB1 hairpin peptide from discrete path sampling
Evans, D. A., & Wales, D. J. (2004) · The Journal of Chemical Physics · doi:10.1063/1.1759317 · Cited by 131 · see citing works
Nguyen, P. H., Stock, G., Mittag, E., Hu, C., & Li, M. S. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20696 · Cited by 129 · see citing works
Residue-Specific α-Helix Propensities from Molecular Simulation
Best, R. B., Sancho, D. D., & Mittal, J. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2012.02.024 · Cited by 123 · see citing works
Self-citationNoé, F., Doose, S., Daidone, I., Löllmann, M., Sauer, M., Chodera, J. D., & Smith, J. C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004646108 · Cited by 116 · see citing works
Best, R. B., & Mittal, J. (2010) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22972 · Cited by 115 · see citing works
Self-citationMittal, J., & Best, R. B. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.05.005 · Cited by 113 · see citing works
Self-citationBalance between α and β Structures in Ab Initio Protein Folding
Best, R. B., & Mittal, J. (2010) · The Journal of Physical Chemistry B · doi:10.1021/jp102575b · Cited by 112 · see citing works
Self-citationMa, B., & Nussinov, R. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3518 · Cited by 110 · see citing works
The Unfolded Ensemble and Folding Mechanism of the C-Terminal GB1 β-Hairpin
Bonomi, M., Branduardi, D., Gervasio, F. L., & Parrinello, M. (2008) · Journal of the American Chemical Society · doi:10.1021/ja803652f · Cited by 97 · see citing works
Understanding the Mechanism of β-Hairpin Folding via φ-Value Analysis
Du, D., Tucker, M. J., & Gai, F. (2006) · Biochemistry · doi:10.1021/bi052039s · Cited by 95 · see citing works
Extremely slow intramolecular diffusion in unfolded protein L
Waldauer, S. A., Bakajin, O., & Lapidus, L. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005415107 · Cited by 92 · see citing works
Hairpin folding rates reflect mutations within and remote from the turn region
Olsen, K. A., Fesinmeyer, R. M., Stewart, J. M., & Andersen, N. H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504392102 · Cited by 88 · see citing works
Protein structural alignments and functional genomics
Irving, J. A., Whisstock, J. C., & Lesk, A. M. (2001) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20010215)42:3 · Cited by 87 · see citing works
Complex folding pathways in a simple β‐hairpin
Wei, G., Mousseau, N., & Derreumaux, P. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20127 · Cited by 87 · see citing works
Unfolded-State Dynamics and Structure of Protein L Characterized by Simulation and Experiment
Voelz, V. A., Singh, V. R., Wedemeyer, W. J., Lapidus, L. J., & Pande, V. S. (2010) · Journal of the American Chemical Society · doi:10.1021/ja908369h · Cited by 85 · see citing works
Fersht, A. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182542699 · Cited by 80 · see citing works
Bowman, G. R. (2012) · The Journal of Chemical Physics · doi:10.1063/1.4755751 · Cited by 76 · see citing works
Culik, R. M., Jo, H., DeGrado, W. F., & Gai, F. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301681v · Cited by 72 · see citing works
What Is the Time Scale for α-Helix Nucleation?
Sancho, D. D., & Best, R. B. (2011) · Journal of the American Chemical Society · doi:10.1021/ja200834s · Cited by 72 · see citing works
Self-citationMicroscopic events in β-hairpin folding from alternative unfolded ensembles
Best, R. B., & Mittal, J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016685108 · Cited by 67 · see citing works
Self-citationEffect of Urea on the β-Hairpin Conformational Ensemble and Protein Denaturation Mechanism
Berteotti, A., Barducci, A., & Parrinello, M. (2011) · Journal of the American Chemical Society · doi:10.1021/ja202849a · Cited by 59 · see citing works
Yoda, T., Sugita, Y., & Okamoto, Y. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21264 · Cited by 56 · see citing works
Analysis of the distributed computing approach applied to the folding of a small β peptide
Paci, E., Cavalli, A., Vendruscolo, M., & Caflisch, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1331838100 · Cited by 45 · see citing works
Evaluation and Optimization of Discrete State Models of Protein Folding
Kellogg, E. H., Lange, O. F., & Baker, D. A. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp3044303 · Cited by 45 · see citing works
Raising the Speed Limit for β-Hairpin Formation
Davis, C. M., Xiao, S., Raleigh, D. P., & Dyer, R. B. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3046734 · Cited by 44 · see citing works
Distinguishing among Structural Ensembles of the GB1 Peptide: REMD Simulations and NMR Experiments
Weinstock, D. S., Narayanan, C., Felts, A. K., Andrec, M., Levy, R. M., Wu, K., & Baum, J. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0677517 · Cited by 23 · see citing works
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Chodera, J. D., & Noé, F. (2014) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2014.04.002 · Cited by 776 · see citing works
Best, R., Zheng, W.-W., & Mittal, J. (2014) · Journal of Chemical Theory and Computation · doi:10.1021/ct500569b · Cited by 312 · see citing works
Self-citationYu, H., Han, W., Ma, W., & Schulten, K. J. (2015) · The Journal of Chemical Physics · doi:10.1063/1.4936910 · Cited by 99 · see citing works
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Best, R. B., & Hummer, G. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520864113 · Cited by 53 · see citing works
Self-citationArsiccio, A., McCarty, J., Pisano, R., & Shea, J. (2018) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.8b07368 · Cited by 51 · see citing works
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Zheng, W., Sancho, D. D., Hoppe, T. A., & Best, R. B. (2015) · Journal of the American Chemical Society · doi:10.1021/ja511609u · Cited by 50 · see citing works
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- Authors
- De Sancho, D., Mittal, J., & Best, R. B.
- Affiliations
- Cambridge University, Department of Chemistry, Lensfield Road Cambridge CB2 1EW, United Kingdom
- Department of Chemical Engineering, 111 Research Drive, Iacocca Hall, Bethlehem, Pennsylvania 18015, United States
- National Institutes of Health (US)
- Corresponding author
- Best, Robert B.
- Venue
- Journal of Chemical Theory and Computation
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-02-07
- Volume
- 9
- Issue
- 3
- Pages
- 1743-1753
- ISSN
- 1549-9618 (ISSN-L)
- 1549-9626
- OpenAlex
- W2327274849
- Cited by
- 35
- References
- 70
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 9 · 2014: 4 · 2013: 3
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Chemical Theory and Computation (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
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
- Keywords
- protein G, folding kinetics, two-state folding, master equation, first passage time distribution, non-exponential kinetics, folding transition state, zipper mechanism, relaxation time
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 ›
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