The nature of folded states of globular proteins

Honeycutt, J. D.; Thirumalai, D.

doi:10.1002/bip.360320610

Cited by 360Protein Structure and DynamicsRNA and protein synthesis mechanismsAdvanced Physical and Chemical Molecular Interactions

The nature of folded states of globular proteins

Honeycutt, J. D., Thirumalai, D.·1992·Biopolymers

DOI 10.1002/bip.360320610

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Abstract

We suggest, using dynamical simulations of a simple heteropolymer modelling the α‐carbon sequence in a protein, that genetically the folded states of globular proteins correspond to statistically well‐defined metastable states. This hypothesis, called the metastability hypothesis, states that there are several free energy minima separated by barriers of various heights such that the folded conformations of a polypeptide chain in each of the minima have similar structural characteristics but have different energies from one another. The calculated structural characteristics, such as bond angle and dihedral angle distribution functions, are assumed to arise from only those configurations belonging to a given minimum. The validity of this hypothesis is illustrated by simulations of a continuum model of a heteropolymer whose low temperature state is a well‐defined β‐barrel structure. The simulations were done using a molecular dynamics algorithm (referred to as the “noisy” molecular dynamics method) containing both friction and noise terms. It is shown that for this model there are several distinct metastable minima in which the structural features are similar. Several new methods of analyzing fluctuations in structures belonging to two distinct minima are introduced. The most notable one is a dynamic measure of compactness that can in principle provide the time required for maximal compactness to be achieved. The analysis shows that for a given metastable state in which the protein has a well‐defined folded structure the transition to a state of higher compactness occurs very slowly, lending credence to the notion that the system encounters a late barrier in the process of folding to the most compact structure. The examination of the fluctuations in the structures near the unfolding → folding transition temperature indicates that the transition state for the unfolding to folding process occurs closer to the folded state.

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Rather than one structure, the native state comprises many conformations that fluctuate at the funnel bottom with similar energies and low barriers.
“Therefore, on the energy landscape, the protein native state is not a single structure but a collection of conformations fluctuating at the bottom of the funnel with comparable energy and small energy barriers.160–161”
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 [161]

Optimization by Simulated Annealing
Kirkpatrick, S., Gelatt, C. D., & Vecchi, M. P. (1983) · Science · doi:10.1126/science.220.4598.671 · Cited by 45,134 · see citing works
Scaling concepts in polymer physics
Gordon, M. (1981) · Polymer · doi:10.1016/0032-3861(81)90183-x · Cited by 10,559 · see citing works
<i>Scaling Concepts in Polymer Physics</i>
de Gennes, P. G., & Witten, T. A. (1980) · Physics Today · doi:10.1063/1.2914118 · Cited by 9,348 · see citing works
Principles that Govern the Folding of Protein Chains
Anfinsen, C. B. (1973) · Science · doi:10.1126/science.181.4096.223 · Cited by 7,096 · see citing works
A computer simulation method for the calculation of equilibrium constants for the formation of physical clusters of molecules: Application to small water clusters
Swope, W. C., Andersen, H. C., Berens, P. H., & Wilson, K. R. (1982) · The Journal of Chemical Physics · doi:10.1063/1.442716 · Cited by 4,068 · see citing works
Dominant forces in protein folding
Dill, K. A. (1990) · Biochemistry · doi:10.1021/bi00483a001 · Cited by 3,824 · see citing works
Spin Glass Theory and Beyond: An Introduction to the Replica Method and Its Applications
Mezard, M., Parisi, G., & Virasoro, M. (1986) · World Scientific Lecture Notes in Physics · doi:10.1142/0271 · Cited by 3,653 · see citing works
The Anatomy and Taxonomy of Protein Structure
Richardson, J. S. (1981) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60520-3 · Cited by 3,378 · see citing works
Molecular dynamics study of melting and freezing of small Lennard-Jones clusters
Honeycutt, J. D., & Andersen, H. C. (1987) · The Journal of Physical Chemistry · doi:10.1021/j100303a014 · Cited by 3,284 · see citing works
Self-citation
Rattle: A “velocity” version of the shake algorithm for molecular dynamics calculations
Andersen, H. C. (1983) · Journal of Computational Physics · doi:10.1016/0021-9991(83)90014-1 · Cited by 3,161 · see citing works
Spin Glass Theory and Beyond
Mézard, M., Giorgio Parisi, A., VIRASORO, M. A., & Thouless, D. J. (1988) · Physics Today · doi:10.1063/1.2811676 · Cited by 2,683 · see citing works
Algorithms for macromolecular dynamics and constraint dynamics
van Gunsteren, W. F., & Berendsen, H. J. C. (1977) · Molecular Physics · doi:10.1080/00268977700102571 · Cited by 1,757 · see citing works
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
Monte Carlo-minimization approach to the multiple-minima problem in protein folding.
Li, Z., & Scheraga, H. A. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.19.6611 · Cited by 1,475 · see citing works
Hidden structure in liquids
Stillinger, F. H., & Weber, T. A. (1982) · Physical Review A · doi:10.1103/physreva.25.978 · Cited by 1,380 · see citing works
The statistical mechanics of polymers with excluded volume
Edwards, S. F. (1965) · Proceedings of the Physical Society · doi:10.1088/0370-1328/85/4/301 · Cited by 1,360 · see citing works
Homologous plant and bacterial proteins chaperone oligomeric protein assembly
Hemmingsen, S. M., Woolford, C. A., van der Vies, S. M., Tilly, K., Dennis, D. T., Georgopoulos, C. P., Hendrix, R. W., & Ellis, R. J. (1988) · Nature · doi:10.1038/333330a0 · Cited by 1,283 · see citing works
Dynamics of Proteins and Nucleic Acids
McCammon, J. A., Harvey, S. C., & Wolynes, P. G. (1988) · Physics Today · doi:10.1063/1.2811564 · Cited by 1,255 · see citing works
Principles of Protein Structure
Schulz, G. E., & Schirmer, R. H. (1979) · Springer advanced texts in chemistry · doi:10.1007/978-1-4612-6137-7 · Cited by 1,109 · see citing works
Principles of protein structure
Schulz, G., & Schirmer, R. H. (1980) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(80)90019-9 · Cited by 1,062 · see citing works
Perspective on the glass transition
Angell, C. A. (1988) · Journal of Physics and Chemistry of Solids · doi:10.1016/0022-3697(88)90002-9 · Cited by 998 · see citing works
Conformational Substates in Proteins
Frauenfelder, H., Parak, F., & Young, R. D. (1988) · Annual Review of Biophysics and Biophysical Chemistry · doi:10.1146/annurev.bb.17.060188.002315 · Cited by 995 · see citing works
Experimental and Theoretical Aspects of Protein Folding
Anfinsen, C. B., & Scheraga, H. A. (1975) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60413-1 · Cited by 973 · see citing works
Protein states and proteinquakes.
Ansari, A., Berendzen, J., Bowne, S. F., Frauenfelder, H., Iben, I. E., Sauke, T. B., Shyamsunder, E., & Young, R. D. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.15.5000 · Cited by 828 · see citing works
Proteins: A Theoretical Perspective of Dynamics, Structure and Thermodynamics
Brooks, C. L., Karplus, M., Pettitt, B. M., & Austin, R. H. (1990) · Physics Today · doi:10.1063/1.2810459 · Cited by 747 · see citing works
Intermediates 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
GroE heat-shock proteins promote assembly of foreign prokaryotic ribulose bisphosphate carboxylase oligomers in Escherichia coli
Goloubinoff, P., Gatenby, A. A., & Lorimer, G. H. (1989) · Nature · doi:10.1038/337044a0 · Cited by 712 · see citing works
Multiple Conformational States of Proteins: A Molecular Dynamics Analysis of Myoglobin
Elber, R., & Karplus, M. (1987) · Science · doi:10.1126/science.3798113 · Cited by 673 · see citing works
Protein-folding dynamics
Karplus, M., & Weaver, D. L. (1976) · Nature · doi:10.1038/260404a0 · Cited by 629 · see citing works
Advances in Chemical Physics
Brooks, C. L., Karplus, M., & Pettitt, B. M. 1. (1988) · Advances in chemical physics · doi:10.1002/9780470141205 · Cited by 502 · see citing works
Accurate simulation of protein dynamics in solution.
Levitt, M., & Sharon, R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.20.7557 · Cited by 451 · see citing works
Principles and Patterns of Protein Conformation
Richardson, J. S., & Richardson, D. C. (1989) · Springer eBooks · doi:10.1007/978-1-4613-1571-1_1 · Cited by 414 · see citing works
The theory and practice of distance geometry
Havel, T. F., Kuntz, I. D., & Crippen, G. M. (1983) · Bulletin of Mathematical Biology · doi:10.1016/s0092-8240(83)80020-2 · Cited by 375 · see citing works
Origins of structure in globular proteins.
Chan, H. S., & Dill, K. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.16.6388 · Cited by 343 · see citing works
Simulations of the Folding of a Globular Protein
Skolnick, J., & Koliński, A. (1990) · Science · doi:10.1126/science.250.4984.1121 · Cited by 318 · see citing works
Metastability of the folded states of globular proteins.
Honeycutt, J. D., & Thirumalai, D. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.9.3526 · Cited by 305 · see citing works
Self-citation
The Genetic Control of Tertiary Protein Structure: Studies With Model SystemsPreprint
Epstein, C. J., Goldberger, R. F., & Anfinsen, C. B. (1963) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1963.028.01.060 · Cited by 304 · see citing works
An analysis of incorrectly folded protein models
Novotný, J., Bruccoleri, R. E., & Karplus, M. (1984) · Journal of Molecular Biology · doi:10.1016/0022-2836(84)90049-4 · Cited by 280 · see citing works
The theory and practice of distance geometry
Havel, T. F., Kuntz, I. D., & Crippen, G. M. (1983) · Bulletin of Mathematical Biology · doi:10.1007/bf02460044 · Cited by 280 · see citing works
Proteins and pressure
Frauenfelder, H., Alberding, N., Ansari, A., Braunstein, D., Cowen, B. R., Hong, M. K., Iben, I. E. T., Johnson, J. B., & Luck, S. (1990) · The Journal of Physical Chemistry · doi:10.1021/j100366a002 · Cited by 278 · see citing works
Acquisition of Three-Dimensional Structure of Proteins
Wetlaufer, D. B., & Ristow, S. S. (1973) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.42.070173.001031 · Cited by 249 · see citing works
Criteria that discriminate between native proteins and incorrectly folded models
Novotný, J., Rashin, A. A., & Bruccoleri, R. E. (1988) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340040105 · Cited by 199 · see citing works
Similarities of protein topologies: evolutionary divergence, functional convergence or principles of folding?
Ptitsyn, O. B., & Finkelstein, A. V. (1980) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500001724 · Cited by 194 · see citing works
Ergodic behavior in supercooled liquids and in glasses
Thirumalai, D., Mountain, R. D., & Kirkpatrick, T. R. (1989) · Physical Review A · doi:10.1103/physreva.39.3563 · Cited by 184 · see citing works
Self-citation
Statistical Physics of Polymer Solutions: Conformation‐Space Renormalization‐Group Approach
Oono, Y. (1985) · Advances in chemical physics · doi:10.1002/9780470142851.ch5 · Cited by 183 · see citing works
Diffusion–collision model for protein folding
Karplus, M., & Weaver, D. L. (1979) · Biopolymers · doi:10.1002/bip.1979.360180608 · Cited by 183 · see citing works
A model of protein conformational substates
Stein, D. L. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.11.3670 · Cited by 151 · see citing works
Toward Protein Tertiary Structure Recognition by Means of Associative Memory Hamiltonians
Friedrichs, M. S., & Wolynes, P. G. (1989) · Science · doi:10.1126/science.246.4928.371 · Cited by 148 · see citing works
Frozen states of a disordered globular heteropolymer
Shakhnovich, E. I., & Gutin, A. M. (1989) · Journal of Physics A Mathematical and General · doi:10.1088/0305-4470/22/10/019 · Cited by 146 · see citing works
The Protein Folding Problem
Richards, F. M. (1991) · Scientific American · doi:10.1038/scientificamerican0191-54 · Cited by 145 · see citing works
Protein folding
GHÉLIS, C. (1982) · Cited by 138 · see citing works
Prediction of the native conformation of a polypeptide by a statistical‐mechanical procedure. I. Backbone structure of enkephalin
Paine, G. H., & Scheraga, H. A. (1985) · Biopolymers · doi:10.1002/bip.360240802 · Cited by 118 · see citing works
Protein folding: deciphering the second half of the genetic code
Dodson, G. G. (1991) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(91)90030-y · Cited by 103 · see citing works
Protein Folding: Deciphering the Second Half of the Genetic Code
Gierasch, L. M., & King, J. E. (1990) · Medical Entomology and Zoology · Cited by 101 · see citing works
The collapse transition of semiflexible polymers. A Monte Carlo simulation of a model system
Koliński, A., Skolnick, J., & Yaris, R. (1986) · The Journal of Chemical Physics · doi:10.1063/1.450930 · Cited by 91 · see citing works
Studies on Ovalbumin II. The Formation and Properties of S-Ovalbumin, a More Stable Form of Ovalbumin
Smith, M., & Back, J. F. (1965) · Australian Journal of Biological Sciences · doi:10.1071/bi9650365 · Cited by 86 · see citing works
Structural basis of hierarchical multiple substates of a protein. I: Introduction
Noguti, T., & Gō, N. (1989) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340050203 · Cited by 82 · see citing works
Spin Glasses and Biology
Stein, D. L. (1992) · Series on directions in condensed matter physics · doi:10.1142/0446 · Cited by 75 · see citing works
Ergodic convergence properties of supercooled liquids and glasses
Thirumalai, D., & Mountain, R. D. (1990) · Physical Review A · doi:10.1103/physreva.42.4574 · Cited by 68 · see citing works
Self-citation
Deciphering the Rules of Protein Folding
King, J. E. (1989) · Chemical & Engineering News · doi:10.1021/cen-v067n015.p032 · Cited by 66 · see citing works
Studies on Ovalbumin I. Denaturation By Heat, and the Heterogeneity of Ovalbumin
Smith, M. (1964) · Australian Journal of Biological Sciences · doi:10.1071/bi9640261 · Cited by 57 · see citing works
Prediction of the native conformation of a polypeptide by a statistical‐mechanical procedure. II. average backbone structure of enkephalin
Paine, G. H., & Scheraga, H. A. (1986) · Biopolymers · doi:10.1002/bip.360250812 · Cited by 45 · see citing works
Monte carlo studies on equilibrium globular protein folding. I. Homopolymeric lattice models of β‐barrel proteins
Koliński, A., Skolnick, J., & Yaris, R. (1987) · Biopolymers · doi:10.1002/bip.360260613 · Cited by 43 · see citing works
Monte carlo studies on equilibrium globular protein folding. III. The four helix bundle
Sikorski, A., & Skolnick, J. (1989) · Biopolymers · doi:10.1002/bip.360280605 · Cited by 39 · see citing works
Monte carlo studies on equilibrium globular protein folding. II. β‐barrel globular protein models
Skolnick, J., Koliński, A., & Yaris, R. (1989) · Biopolymers · doi:10.1002/bip.360280604 · Cited by 33 · see citing works
Metal ion binding properties of hen ovalbumin and S-ovalbumin: characterization of the metal ion binding site by phosphorus-31 NMR and water proton relaxation rate enhancements
Goux, W. J., & Venkatasubramanian, P. N. (1986) · Biochemistry · doi:10.1021/bi00349a013 · Cited by 33 · see citing works
Dynamic monte carlo simulations of globular protein folding
Sikorski, A., & Skolnick, J. (1990) · Journal of Molecular Biology · doi:10.1016/s0022-2836(05)80103-2 · Cited by 27 · see citing works
Studies on Ovalbumin. IV. Trypsin Digsestion and the Cystine Peptides of Ovalbumin and S-Ovalbumin
Smith, M., & Back, J. F. (1968) · Australian Journal of Biological Sciences · doi:10.1071/bi9680549 · Cited by 17 · see citing works
Flavonoids from Prunus persica Batsch (peach bark)
Rahman, W., & Bhatnagar, S. (1968) · Australian Journal of Chemistry · doi:10.1071/ch9680539 · Cited by 15 · see citing works
Conformational Energy Calculations on Polypeptides and Proteins: Use of a Statistical Mechanical Procedure for Evaluating Structure and Propertiesa
Scheraga, H. A., & Paine, G. H. (1986) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1986.tb20937.x · Cited by 11 · see citing works

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Funnels, pathways, and the energy landscape of protein folding: A synthesis
Bryngelson, J. D., Onuchic, J. N., Socci, N. D., & Wolynes, P. G. (1995) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.340210302 · Cited by 2,648 · see citing works
THEORY OF PROTEIN FOLDING: The Energy Landscape Perspective
Onuchic, J. N., Luthey-Schulten, Z., & Wolynes, P. G. (1997) · Annual Review of Physical Chemistry · doi:10.1146/annurev.physchem.48.1.545 · Cited by 2,210 · 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
Theory of protein folding
Onuchic, J. N., & Wolynes, P. G. (2004) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2004.01.009 · Cited by 1,298 · see citing works
Speeding molecular recognition by using the folding funnel: The fly-casting mechanism
Shoemaker, B. A., Portman, J. J., & Wolynes, P. G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160259697 · Cited by 971 · see citing works
How does a protein fold?
Šali, A., Shakhnovich, E. I., & Karplus, M. (1994) · Nature · doi:10.1038/369248a0 · Cited by 944 · see citing works
The topology of multidimensional potential energy surfaces: Theory and application to peptide structure and kinetics
Becker, O. M., & Karplus, M. (1997) · The Journal of Chemical Physics · doi:10.1063/1.473299 · Cited by 808 · see citing works
Molecular crowding enhances native state stability and refolding rates of globular proteins
Cheung, M. S., Klimov, D. K., & Thirumalai, D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409630102 · Cited by 557 · see citing works
Self-citation
Non-globular domains in protein sequences: Automated segmentation using complexity measures
Wootton, J. C. (1994) · Computers & Chemistry · doi:10.1016/0097-8485(94)85023-2 · Cited by 524 · see citing works
Engineering of stable and fast-folding sequences of model proteins.
Shakhnovich, E. I., & Gutin, A. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.15.7195 · Cited by 516 · see citing works
F<scp>ROM</scp>F<scp>OLDING</scp>T<scp>HEORIES TO</scp>F<scp>OLDING</scp>P<scp>ROTEINS</scp>: A Review and Assessment of Simulation Studies of Protein Folding and Unfolding
Shea, J.-E., & Brooks III, C. L. (2001) · Annual Review of Physical Chemistry · doi:10.1146/annurev.physchem.52.1.499 · Cited by 481 · see citing works
Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell
Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436 · see citing works
Protein folding in the landscape perspective: Chevron plots and non-arrhenius kinetics
Chan, H. S., & Dill, K. A. (1998) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19980101)30:1 · Cited by 433 · see citing works
Protein folding kinetics: timescales, pathways and energy landscapes in terms of sequence-dependent properties
Veitshans, T., Klimov, D., & Thirumalai, D. (1997) · Folding and Design · doi:10.1016/s1359-0278(97)00002-3 · Cited by 397 · see citing works
Self-citation
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
Self-citation
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
Self-citation
Coarse-grained models of protein folding: toy models or predictive tools?
Clementi, C. (2007) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2007.10.005 · Cited by 335 · see citing works
Protein folding funnels: the nature of the transition state ensemble
Onuchic, J. N., Socci, N. D., Luthey-Schulten, Z. A., & Wolynes, P. G. (1996) · Folding and Design · doi:10.1016/s1359-0278(96)00060-0 · Cited by 330 · see citing works
Folding funnels and frustration in off-lattice minimalist protein landscapes
Nymeyer, H., Garcı́a, A. E., & Onuchic, J. N. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.5921 · Cited by 323 · see citing works
Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations
Okazaki, 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 Protein Folding Problem
Chan, H. S., & Dill, K. A. (1993) · Physics Today · doi:10.1063/1.881371 · Cited by 308 · see citing works
The nature of protein folding pathways: The classical versus the new view
Baldwin, R. L. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00208801 · Cited by 307 · 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
Transition states and folding dynamics of proteins and heteropolymers
Chan, H. S., & Dill, K. A. (1994) · The Journal of Chemical Physics · doi:10.1063/1.466677 · Cited by 281 · 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
Constant temperature simulations using the Langevin equation with velocity Verlet integration
Paterlini, M., & Ferguson, D. M. (1998) · Chemical Physics · doi:10.1016/s0301-0104(98)00214-6 · Cited by 232 · see citing works
CafeMol: A Coarse-Grained Biomolecular Simulator for Simulating Proteins at Work
Kenzaki, H., Koga, N., Hori, N., Kanada, R., Li, W., Okazaki, K.-I., Yao, X., & Takada, S. (2011) · Journal of Chemical Theory and Computation · doi:10.1021/ct2001045 · Cited by 232 · see citing works
How protein thermodynamics and folding mechanisms are altered by the chaperonin cage: Molecular simulations
Takagi, F., Koga, N., & Takada, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1831920100 · Cited by 218 · see citing works
Energy Landscapes: From Clusters to Biomolecules
Wales, D. J., Doye, J. P. K., Miller, M. A., Mortenson, P. N., & Walsh, T. R. (2000) · Advances in chemical physics · doi:10.1002/9780470141748.ch1 · Cited by 204 · see citing works
Understanding protein folding with energy landscape theory Part I: Basic concepts
Plotkin, S. S., & Onuchic, J. N. (2002) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583502003761 · Cited by 199 · see citing works
Criterion that Determines the Foldability of Proteins
Klimov, D. K., & Thirumalai, D. (1996) · Physical Review Letters · doi:10.1103/physrevlett.76.4070 · Cited by 197 · see citing works
Self-citation
Simple model of protein folding kinetics.
Zwanzig, R. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.21.9801 · Cited by 194 · see citing works
Reduced models of proteins and their applications
Koliński, A., & Skolnick, J. (2003) · Polymer · doi:10.1016/j.polymer.2003.10.064 · Cited by 190 · see citing works
Energy landscapes: calculating pathways and rates
Wales, D. J. (2006) · International Reviews in Physical Chemistry · doi:10.1080/01442350600676921 · Cited by 184 · see citing works
The energy landscape as a unifying theme in molecular science
Wales, D. J. (2004) · Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences · doi:10.1098/rsta.2004.1497 · Cited by 176 · see citing works
Molecular Modeling of Proteins and Mathematical Prediction of Protein Structure
Neumaier, A. (1997) · SIAM Review · doi:10.1137/s0036144594278060 · Cited by 173 · see citing works
Deciphering the timescales and mechanisms of protein folding using minimal off-lattice models
Thirumalai, D., & Klimov, D. K. (1999) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(99)80028-1 · Cited by 161 · see citing works
Self-citation
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Clementi, C., & Plotkin, S. S. (2004) · Protein Science · doi:10.1110/ps.03580104 · Cited by 158 · see citing works
Conformational Polymorphism of Amphiphilic Polymers in a Poor Solvent
Vasilevskaya, V. V., Khalatur, P. G., & Khokhlov, A. R. (2003) · Macromolecules · doi:10.1021/ma0350563 · Cited by 153 · see citing works
Interphase human chromosome exhibits out of equilibrium glassy dynamics
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Self-citation
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Solvent Viscosity and Friction in Protein Folding Dynamics
Hagen, S. J. (2010) · Current Protein and Peptide Science · doi:10.2174/138920310791330596 · Cited by 145 · see citing works
The folding thermodynamics and kinetics of crambin using an all-atom monte carlo simulation11Edited by A. R. Fersht
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Internal strain regulates the nucleotide binding site of the kinesin leading head
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Self-citation
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Camacho, C. J., & Thirumalai, D. (1993) · Physical Review Letters · doi:10.1103/physrevlett.71.2505 · Cited by 134 · see citing works
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Self-citation
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Self-citation
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Self-citation
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Energy landscape of a model protein
Miller, M. A., & Wales, D. J. (1999) · The Journal of Chemical Physics · doi:10.1063/1.480011 · Cited by 107 · see citing works
Multiscale Ensemble Modeling of Intrinsically Disordered Proteins: p53 N-Terminal Domain
Terakawa, T., & Takada, S. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.08.003 · Cited by 105 · see citing works
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Thirumalai, D., Hyeon, C., Zhuravlev, P. I., & Lorimer, G. H. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00760 · Cited by 105 · see citing works
Self-citation
Generalized Yvon-Born-Green Theory for Molecular Systems
Mullinax, J. W., & Noid, W. G. (2009) · Physical Review Letters · doi:10.1103/physrevlett.103.198104 · Cited by 103 · see citing works
Folding of a model three-helix bundle protein: a thermodynamic and kinetic analysis 1 1Edited by A. R. Fersht
Zhou, Y., & Karplus, M. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2936 · Cited by 103 · see citing works
Self-assembly of β-sheet forming peptides into chiral fibrillar aggregates
Bellesia, G., & Shea, J. (2007) · The Journal of Chemical Physics · doi:10.1063/1.2739547 · Cited by 101 · see citing works
Condensates in RNA repeat sequences are heterogeneously organized and exhibit reptation dynamics
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Self-citation
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Das, P., Matysiak, S., & Clementi, C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409471102 · Cited by 100 · see citing works
D/H amide kinetic isotope effects reveal when hydrogen bonds form during protein folding.
Sosnick, T. R., Krantz, B. A., Moran, L. B., & Kentsis, A. (2000) · Nature Structural Biology · doi:10.1038/71265 · Cited by 99 · 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
Exploring the space of protein folding Hamiltonians: The balance of forces in a minimalist β-barrel model
Shea, J., Nochomovitz, Y. D., Guo, Z., & Brooks, C. L. (1998) · The Journal of Chemical Physics · doi:10.1063/1.476842 · Cited by 95 · see citing works
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A review of combined experimental and computational procedures for assessing biopolymer structure–process–property relationships
Gronau, G., Krishnaji, S. T., Kinahan, M. E., Giesa, T., Wong, J. Y., Kaplan, D. L., & Buehler, M. J. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.06.054 · Cited by 88 · see citing works
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Self-citation
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Self-citation
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Self-citation
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Eastwood, M. P., & Wolynes, P. G. (2001) · The Journal of Chemical Physics · doi:10.1063/1.1315994 · Cited by 83 · see citing works
Multi-basin dynamics of a protein in a crystal environment
Garcı́a, A. E., Blumenfeld, R., Hummer, G., & KRUMHANSL, J. A. (1997) · Physica D Nonlinear Phenomena · doi:10.1016/s0167-2789(97)00090-0 · Cited by 83 · see citing works
Regulation of the H4 tail binding and folding landscapes via Lys-16 acetylation
Potoyan, D. A., & Papoian, G. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201805109 · Cited by 82 · see citing works
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Shea, J., Onuchic, J. N., & Brooks, C. L. (2000) · The Journal of Chemical Physics · doi:10.1063/1.1313792 · Cited by 81 · see citing works
Effects of confinement and crowding on the thermodynamics and kinetics of folding of a minimalist β-barrel protein
Friedel, M., Sheeler, D. J., & Shea, J. (2003) · The Journal of Chemical Physics · doi:10.1063/1.1564048 · Cited by 80 · see citing works
Energy landscapes, global optimization and dynamics of the polyalanine Ac(ala)8NHMe
Mortenson, P. N., & Wales, D. J. (2001) · The Journal of Chemical Physics · doi:10.1063/1.1343486 · Cited by 79 · see citing works
Linking topography of its potential surface with the dynamics of folding of a protein model
Berry, R. S., Elmacı, N., Rose, J. P., & Vekhter, B. G. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9520 · Cited by 79 · see citing works
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Nguyen, H. T., Hori, N., & Thirumalai, D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911632116 · Cited by 78 · see citing works
Self-citation
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Wallqvist, A., & Ullner, M. (1994) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340180308 · Cited by 78 · see citing works
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Liu, L., Shi, G., Thirumalai, D., & Hyeon, C. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006617 · Cited by 77 · see citing works
Self-citation
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Kiefhaber, T., & Baldwin, R. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.2657 · Cited by 77 · see citing works
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Cheung, M. S., & Thirumalai, D. (2007) · The Journal of Physical Chemistry B · doi:10.1021/jp068201y · Cited by 76 · see citing works
Self-citation
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Röder, K., Joseph, J. A., Husic, B. E., & Wales, D. J. (2019) · Advanced Theory and Simulations · doi:10.1002/adts.201800175 · Cited by 74 · see citing works
Global Optimization: Quantum Thermal Annealing with Path Integral Monte Carlo
Lee, Y.-H., & Berne, B. J. (1999) · The Journal of Physical Chemistry A · doi:10.1021/jp991868i · Cited by 73 · see citing works
The nucleation-collapse mechanism in protein folding: evidence for the non-uniqueness of the folding nucleus
Guo, Z., & Thirumalai, D. (1997) · Folding and Design · doi:10.1016/s1359-0278(97)00052-7 · Cited by 73 · see citing works
Self-citation
Computer simulations of the translocation and unfolding of a protein pulled mechanically through a pore
Huang, L., Kırmızıaltın, S., & Makarov, D. E. (2005) · The Journal of Chemical Physics · doi:10.1063/1.2008231 · Cited by 72 · see citing works
Topography of the free-energy landscape probed via mechanical unfolding of proteins
Kırmızıaltın, S., Huang, L., & Makarov, D. E. (2005) · The Journal of Chemical Physics · doi:10.1063/1.1931659 · Cited by 71 · see citing works
Searching for foldable protein structures using optimized energy functions
Govindarajan, S., & Goldstein, R. A. (1995) · Biopolymers · doi:10.1002/bip.360360105 · Cited by 70 · see citing works
Protein aggregation in silico
Cellmer, T., Bratko, D., Prausnitz, J. M., & Blanch, H. W. (2007) · Trends in biotechnology · doi:10.1016/j.tibtech.2007.03.011 · Cited by 69 · see citing works
Differences in the free energies between the excited states of A β 40 and A β 42 monomers encode their aggregation propensities
Chakraborty, D., Straub, J. E., & Thirumalai, D. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002570117 · Cited by 69 · see citing works
Self-citation
Semiflexible chains in confined spaces
Morrison, G., & Thirumalai, D. (2009) · Physical Review E · doi:10.1103/physreve.79.011924 · Cited by 68 · see citing works
Self-citation
Role of Hydrophobic Hydration in Protein Stability: A 3D Water-Explicit Protein Model Exhibiting Cold and Heat Denaturation
Matysiak, S., Debenedetti, P. G., & Rossky, P. J. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp3039175 · Cited by 66 · see citing works
Sequence-Dependent Three Interaction Site Model for Single- and Double-Stranded DNA
Chakraborty, D., Hori, N., & Thirumalai, D. (2018) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.8b00091 · Cited by 65 · see citing works
Self-citation
Scaling behavior of some molecular shape descriptors of polymer chains and protein backbones
Arteca, G. A. (1994) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.49.2417 · Cited by 65 · see citing works
Overcrossing spectra of protein backbones: Characterization of three‐dimensional molecular shape and global structural homologies
Arteca, G. A. (1993) · Biopolymers · doi:10.1002/bip.360331209 · Cited by 64 · see citing works
From Hi-C Contact Map to Three-Dimensional Organization of Interphase Human Chromosomes
Shi, G., & Thirumalai, D. (2021) · Physical Review X · doi:10.1103/physrevx.11.011051 · Cited by 63 · see citing works
Self-citation
Effect of Finite Size on Cooperativity and Rates of Protein Folding
Kouza, M., Li, M. S., O’Brien, E. P., Hu, C., & Thirumalai, D. (2005) · The Journal of Physical Chemistry A · doi:10.1021/jp053770b · Cited by 63 · see citing works
Self-citation

Metastability of the folded states of globular proteins.
Honeycutt, J. D., & Thirumalai, D. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.9.3526 · Cited by 305 · see citing works
Self-citation
Identifying metastable states of folding proteins
Jain, A., & Stock, G. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300077q · Cited by 75 · see citing works
A metastable state in folding simulations of a protein model
Dinner, A. R., & Karplus, M. (1998) · Nature Structural Biology · doi:10.1038/nsb0398-236 · Cited by 35 · see citing works
Metastable states and folding free energy barriers
Baker, D. A. (1998) · Nature Structural Biology · doi:10.1038/4130 · Cited by 42 · see citing works
Kinematics and thermodynamics of a folding heteropolymer.
Fukugita, M., Lancaster, D., & Mitchard, M. G. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.6365 · Cited by 31 · see citing works

Authors: Honeycutt, J. D., & Thirumalai, D.
Affiliations: University of Maryland, College Park (US)
ORCID: Thirumalai, D.
Venue: Biopolymers
Publisher: Wiley
Published: 1992-06
Volume: 32
Issue: 6
Pages: 695-709
ISSN: 0006-3525 (ISSN-L)
1097-0282
DOI: 10.1002/bip.360320610
OpenAlex: W2153333215
Cited by: 360
References: 71
Citations by year: 2026: 4 · 2025: 3 · 2024: 9 · 2023: 3 · 2022: 7 · 2021: 3 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 3 · 2016: 13 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 9
FWCI: 5.03
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4262 d)
Locations: Biopolymers (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 folding, metastable states, free energy minima, beta-barrel, protein compactness, transition state, conformational fluctuations, dihedral angle distribution
MeSH terms: Algorithms, Mathematics, Models, Molecular, Models, Theoretical, Protein Conformation, Proteins, Thermodynamics

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The nature of folded states of globular proteins

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