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Protein functional landscapes, dynamics, allostery: a tortuous path towards a universal theoretical framework

Published online by Cambridge University Press:  07 September 2010

Pavel I. Zhuravlev  and
Garegin A. Papoian
Pavel I. Zhuravlev
Affiliation:
Department of Chemistry and Biochemistry, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
Garegin A. Papoian*
Affiliation:
Department of Chemistry and Biochemistry, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
*
*Author for Correspondence: G. A. Papoian, Monroe Martin Associate Professor, Department of Chemistry and Biochemistry, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA. Tel.: 301-405-8667; Fax: 301-314-9121; E-mail: gpapoian@umd.edu
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Abstract

Energy landscape theories have provided a common ground for understanding the protein folding problem, which once seemed to be overwhelmingly complicated. At the same time, the native state was found to be an ensemble of interconverting states with frustration playing a more important role compared to the folding problem. The landscape of the folded protein – the native landscape – is glassier than the folding landscape; hence, a general description analogous to the folding theories is difficult to achieve. On the other hand, the native basin phase volume is much smaller, allowing a protein to fully sample its native energy landscape on the biological timescales. Current computational resources may also be used to perform this sampling for smaller proteins, to build a ‘topographical map’ of the native landscape that can be used for subsequent analysis. Several major approaches to representing this topographical map are highlighted in this review, including the construction of kinetic networks, hierarchical trees and free energy surfaces with subsequent structural and kinetic analyses. In this review, we extensively discuss the important question of choosing proper collective coordinates characterizing functional motions. In many cases, the substates on the native energy landscape, which represent different functional states, can be used to obtain variables that are well suited for building free energy surfaces and analyzing the protein's functional dynamics. Normal mode analysis can provide such variables in cases where functional motions are dictated by the molecule's architecture. Principal component analysis is a more expensive way of inferring the essential variables from the protein's motions, one that requires a long molecular dynamics simulation. Finally, the two popular models for the allosteric switching mechanism, ‘preexisting equilibrium’ and ‘induced fit’, are interpreted within the energy landscape paradigm as extreme points of a continuum of transition mechanisms. Some experimental evidence illustrating each of these two models, as well as intermediate mechanisms, is presented and discussed.

Type
Review Article
Information
Quarterly Reviews of Biophysics , Volume 43 , Issue 3 , August 2010 , pp. 295 - 332
Copyright
Copyright © Cambridge University Press 2010

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References

7. References

Adcock, S. A. & McCammon, J. A. (2006). Molecular dynamics: survey of methods for simulating the activity of proteins. Chemical Reviews 106, 1589–1615.CrossRefGoogle ScholarPubMed
Alexandrov, V., Lehnert, U., Echols, N., Milburn, D., Engelman, D. & Gerstein, M. (2005). Normal modes for predicting protein motions: a comprehensive database assessment and associated web tool. Protein Science 14, 633–643.CrossRefGoogle ScholarPubMed
Antoine, M., Boutin, J. A. & Ferry, G. (2009). Binding kinetics of glucose and allosteric activators to human glucokinase reveal multiple conformational states. Biochemistry 48, 5466–5482.CrossRefGoogle ScholarPubMed
Arora, K. & Brooks, C. L. (2007). Large-scale allosteric conformational transitions of adenylate kinase appear to involve a population-shift mechanism. Proceedings of the National Academy of Sciences, USA 104, 18496–18501.CrossRefGoogle ScholarPubMed
Austin, R. H., Beeson, K. W., Eisenstein, L., Frauenfelder, H. & Gunsalus, I. C. (1975). Dynamics of ligand binding to myoglobin. Biochemistry 14, 5355–5373.CrossRefGoogle ScholarPubMed
Ayers, S. D., Nedrow, K. L., Gillilan, R. E. & Noy, N. (2007). Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPAR gamma by FABP4. Biochemistry 46, 6744–6752.CrossRefGoogle ScholarPubMed
Bae, S.-H., Legname, G., Serban, A., Prusiner, S. B., Wright, P. E. & Dyson, H. J. (2009). Prion proteins with pathogenic and protective mutations show similar structure and dynamics. Biochemistry 48, 8120–8128.Google Scholar
Bahar, I. & Rader, A. J. (2005). Coarse-grained normal mode analysis in structural biology. Current Opinion in Structural Biology 15, 586–592.Google Scholar
Benkovic, S. & Hammes-Schiffer, S. (2003). A perspective on enzyme catalysis. Science 301, 1196–1202.Google Scholar
Benkovic, S. J., Hammes, G. G. & Hammes-Schiffer, S. (2008). Free-energy landscape of enzyme catalysis. Biochemistry 47, 3317–3321.CrossRefGoogle ScholarPubMed
Berezhkovskii, A. M., Hummer, G. & Szabo, A. (2009). Reactive flux and folding pathways in network models of coarse-grained protein dynamics. Journal of Chemical Physics 130, 205102.Google Scholar
Best, R. B., Chen, Y.-G. & Hummer, G. (2005). Slow protein conformational dynamics from multiple experimental structures: the helix/sheet transition of arc repressor. Structure 13, 1755–1763.CrossRefGoogle ScholarPubMed
Bryngelson, J. D. & Wolynes, P. G. (1987). Spin glasses and the statistical mechanics of protein folding. Proceedings of the National Academy of Sciences, USA 84, 7524–7528.CrossRefGoogle ScholarPubMed
Bryngelson, J. D., Onuchic, J. N., Socci, N. D. & Wolynes, P. G. (1995). Funnels, pathways, and the energy landscape of protein folding: a synthesis. Proteins 21, 167–195.Google Scholar
Buchete, N.-V. & Hummer, G. (2008). Coarse master equations for peptide folding dynamics. Journal of Physical Chemistry B 112, 6057–6069.CrossRefGoogle ScholarPubMed
Caflisch, A. (2006). Network and graph analyses of folding free energy surfaces. Current Opinion in Structural Biology 16, 71–78.CrossRefGoogle ScholarPubMed
Chen, J. & Brooks, C. L. (2007). Can molecular dynamics simulations provide high-resolution refinement of protein structure? Proteins 67, 922–930.CrossRefGoogle ScholarPubMed
Chen, Y., Ding, F., Nie, H., Serohijos, A. W., Sharma, S., Wilcox, K. C., Yin, S. & Dokholyan, N. V. (2008). Protein folding: then and now. Archives in Biochemistry and Biophysics 469, 4–19.CrossRefGoogle ScholarPubMed
Cheung, M. S., García, A. E. & Onuchic, J. N. (2002). Protein folding mediated by solvation: water expulsion and formation of the hydrophobic core occur after the structural collapse. Proceedings of the National Academy of Sciences, USA 99, 685–690.CrossRefGoogle ScholarPubMed
Chi, C. N., Elfstrom, L., Shi, Y., Snall, T., Engstrom, A. & Jemth, P. (2008). Reassessing a sparse energetic network within a single protein domain. Proceedings of the National Academy of Sciences, USA 105, 4679–4684.Google Scholar
Chodera, J. D., Singhal, N., Pande, V. S., Dill, K. A. & Swope, W. C. (2007). Automatic discovery of metastable states for the construction of Markov models of macromolecular conformational dynamics. Journal of Chemical Physics 126, 155101.CrossRefGoogle ScholarPubMed
Chuang, J., Grosberg, A. Y. & Kardar, M. (2001). Free energy self-averaging in protein-sized random heteropolymers. Physical Review Letters 87, 078104.CrossRefGoogle ScholarPubMed
Clarkson, M. W., Gilmore, S. A., Edgell, M. H. & Lee, A. L. (2006). Dynamic coupling and allosteric behavior in a nonallosteric protein. Biochemistry 45, 7693–7699.CrossRefGoogle Scholar
Clore, G. M. (2008). Visualizing lowly-populated regions of the free energy landscape of macromolecular complexes by paramagnetic relaxation enhancement. Molecular Biosystems 4, 1058–1069.CrossRefGoogle ScholarPubMed
Cukier, R. I. (2009). Apo adenylate kinase encodes its holo form: a principal component and varimax analysis. Journal of Physical Chemistry B 113, 1662–1672.CrossRefGoogle Scholar
Das, P., Moll, M., Stamati, H., Kavraki, L. E. & Clementi, C. (2006). Low-dimensional, free-energy landscapes of protein-folding reactions by nonlinear dimensionality reduction. Proceedings of the National Academy of Sciences, USA 103, 9885–9890.Google Scholar
Datta, D., Scheer, J. M., Romanowski, M. J. & Wells, J. A. (2008). An allosteric circuit in caspase-1. Journal of Molecular Biology 381, 1157–1167.CrossRefGoogle ScholarPubMed
Debenedetti, P. & Stillinger, F. (2001). Supercooled liquids and the glass transition. Nature 410, 259–267.Google Scholar
Derrida, B. (1985). A generalization of the random energy model which includes correlations between energies. Journal of Physics Letters – Paris 46, 401–407.CrossRefGoogle Scholar
Dhulesia, A., Gsponer, J. & Vendruscolo, M. (2008). Mapping of two networks of residues that exhibit structural and dynamical changes upon binding in a PDZ domain protein. Journal of the American Chemical Society 130, 8931–8939.CrossRefGoogle Scholar
Dill, K. A. & Chan, H. S. (1997). From Levinthal to pathways to funnels. Nature Structural and Molecular Biology 4, 10–19.Google Scholar
Dill, K. A., Ozkan, S. B., Shell, M. S. & Weikl, T. R. (2008). The protein folding problem. Annual Review of Biophysics 37, 289–316.CrossRefGoogle ScholarPubMed
Dobson, C. M., Sali, A. & Karplus, M. (1998). Protein folding: a perspective from theory and experiment. Angewandte Chemie International Edition 37, 868–893.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Dror, R. O., Arlow, D. H., Borhani, D. W., Jensen, M. Ø., Piana, S. & Shaw, D. E. (2009). Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations. Proceedings of the National Academy of Sciences, USA 106, 4689–4694.CrossRefGoogle ScholarPubMed
Dyson, H. J., Wright, P. E. & Scheraga, H. A. (2006). The role of hydrophobic interactions in initiation and propagation of protein folding. Proceedings of the National Academy of Sciences, USA 103, 13057–13061.CrossRefGoogle ScholarPubMed
Eaton, W. A., Henry, E. R., Hofrichter, J. & Mozzarelli, A. (1999). Is cooperative oxygen binding by hemoglobin really understood? Nature Structural and Molecular Biology 6, 351–358.CrossRefGoogle ScholarPubMed
Ebbinghaus, S., Kim, S. J., Heyden, M., Yu, X., Gruebele, M., Leitner, D. M. & Havenith, M. (2008). Protein sequence- and pH-dependent hydration probed by terahertz spectroscopy. Journal of the American Chemical Society 130, 2374–2375.CrossRefGoogle ScholarPubMed
Eyal, E., Chennubhotla, C., Yang, L.-W. & Bahar, I. (2007). Anisotropic fluctuations of amino acids in protein structures: insights from X-ray crystallography and elastic network models. Bioinformatics 23, i175–i184.Google Scholar
Fang, C., Frontiera, R. R., Tran, R. & Mathies, R. A. (2009). Mapping GFP structure evolution during proton transfer with femtosecond Raman spectroscopy. Nature 462, 200–204.CrossRefGoogle ScholarPubMed
Fenimore, P. W., Frauenfelder, H., McMahon, B. H. & Young, R. D. (2004). Bulk-solvent and hydration-shell fluctuations, similar to alpha- and beta-fluctuations in glasses, control protein motions and functions. Proceedings of the National Academy of Sciences, USA 101, 14408–14413.CrossRefGoogle ScholarPubMed
Ferreiro, D. U., Hegler, J. A., Komives, E. A. & Wolynes, P. G. (2007). Localizing frustration in native proteins and protein assemblies. Proceedings of the National Academy of Sciences, USA 104, 19819–19824.Google Scholar
Fetler, L., Kantrowitz, E. R. & Vachette, P. (2007). Direct observation in solution of a preexisting structural equilibrium for a mutant of the allosteric aspartate transcarbamoylase. Proceedings of the National Academy of Sciences, USA 104, 495–500.CrossRefGoogle ScholarPubMed
Fraser, J. S., Clarkson, M. W., Degnan, S. C., Erion, R., Kern, D. & Alber, T. (2009). Hidden alternative structures of proline isomerase essential for catalysis. Nature 462, 669–673.Google Scholar
Frauenfelder, H. & McMahon, B. (1998). Dynamics and function of proteins: the search for general concepts. Proceedings of the National Academy of Sciences, USA 95, 4795–4797.Google Scholar
Frauenfelder, H., Parak, F. & Young, R. D. (1988). Conformational substates in proteins. Annual Review of Biophysics and Biophysical Chemistry 17, 451–479.CrossRefGoogle ScholarPubMed
Frauenfelder, H., Alberding, N. A., Ansari, A., Braunstein, D., Cowen, B. R., Hong, M. K., Iben, I. E. T., Johnson, J. B. & Luck, S. (1990). Proteins and pressure. Journal of Physical Chemistry 94, 1024–1037.Google Scholar
Frauenfelder, H., Sligar, S. G. & Wolynes, P. G. (1991). The energy landscapes and motions of proteins. Science 254, 1598–1603.CrossRefGoogle ScholarPubMed
Frauenfelder, H., Fenimore, P. W. & Young, R. D. (2007). Protein dynamics and function: insights from the energy landscape and solvent slaving. IUBMB Life 59, 506–512.Google Scholar
Fuentes, E., Der, C. & Lee, A. (2004). Ligand-dependent dynamics and intramolecular signaling in a PDZ domain. Journal of Molecular Biology 335, 1105–1115.Google Scholar
García, A. (1992). Large-amplitude nonlinear motions in proteins. Physical Review Letters 68, 2696–2699.CrossRefGoogle ScholarPubMed
García, A. E. & Sanbonmatsu, K. Y. (2001). Exploring the energy landscape of a beta hairpin in explicit solvent. Proteins 42, 345–354.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Gast, K., Damaschun, H., Misselwitz, R., Mller-Frohne, M., Zirwer, D. & Damaschun, G. (1994). Compactness of protein molten globules: temperature-induced structural changes of the apomyoglobin folding intermediate. European Biophysics Journal 23, 297–305.Google Scholar
Geissler, P. L., Shakhnovich, E. I. & Grosberg, A. Y. (2004). Solvation versus freezing in a heteropolymer globule. Physical Review E, Statistical, Nonlinear, and Softmatter Physics 70, 021802.CrossRefGoogle Scholar
Gianni, S., Walma, T., Arcovito, A., Calosci, N., Bellelli, A., Engstrom, A., Travaglini-Allocatelli, C., Brunori, M., Jemth, P. & Vuister, G. W. (2006). Demonstration of long-range interactions in a PDZ domain by NMR, kinetics, and protein engineering. Structure 14, 1801–1809.CrossRefGoogle Scholar
Grant, B. J., Gorfe, A. A. & McCammon, J. A. (2009). RAS conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics. PLoS Computational Biology 5, e1000325.CrossRefGoogle ScholarPubMed
Guo, Z. & Thirumalai, D. (1995). Kinetics of protein folding: nucleation mechanism, time scales, and pathways. Biopolymers 36, 83–102.CrossRefGoogle Scholar
Hayward, S. & Go, N. (1995). Collective variable description of native protein dynamics. Annual Review of Physical Chemistry 46, 223–250.CrossRefGoogle ScholarPubMed
He, Y., Ku, P. I., Knab, J. R., Chen, J. Y. & Markelz, A. G. (2008). Protein dynamical transition does not require protein structure. Physical Review Letters 101, 178103.Google Scholar
Head-Gordon, T. & Brown, S. (2003). Minimalist models for protein folding and design. Current Opinion in Structural Biology 13, 160–167.Google Scholar
Heath, A. P., Kavraki, L. E. & Clementi, C. (2007). From coarse-grain to all-atom: toward multiscale analysis of protein landscapes. Proteins 68, 646–661.CrossRefGoogle ScholarPubMed
Hegler, J. A., Weinkam, P. & Wolynes, P. G. (2008). The spectrum of biomolecular states and motions. HFSP Journal 2, 307–313.Google Scholar
Henzler-Wildman, K. & Kern, D. (2007). Dynamic personalities of proteins. Nature 450, 964–972.CrossRefGoogle ScholarPubMed
Henzler-Wildman, K. A., Lei, M., Thai, V., Kerns, S. J., Karplus, M. & Kern, D. (2007a). A hierarchy of timescales in protein dynamics is linked to enzyme catalysis. Nature 450, 913–916.CrossRefGoogle ScholarPubMed
Henzler-Wildman, K. A., Thai, V., Lei, M., Ott, M., Wolf-Watz, M., Fenn, T., Pozharski, E., Wilson, M. A., Petsko, G. A., Karplus, M., Hubner, C. G. & Kern, D. (2007b). Intrinsic motions along an enzymatic reaction trajectory. Nature 450, 838–844.CrossRefGoogle ScholarPubMed
Hilser, V. J., Dowdy, D., Oas, T. G. & Freire, E. (1998). The structural distribution of cooperative interactions in proteins: analysis of the native state ensemble. Proceedings of the National Academy of Sciences, USA 95, 9903–9908.CrossRefGoogle ScholarPubMed
Hinrichs, N. S. & Pande, V. S. (2007). Calculation of the distribution of eigenvalues and eigenvectors in Markovian state models for molecular dynamics. Journal of Chemical Physics 126, 244101.CrossRefGoogle ScholarPubMed
Honeycutt, J. D. & Thirumalai, D. (1992). The nature of folded states of globular proteins. Biopolymers 32, 695–709.CrossRefGoogle ScholarPubMed
Hori, N., Chikenji, G., Berry, R. S. & Takada, S. (2009). Folding energy landscape and network dynamics of small globular proteins. Proceedings of the National Academy of Sciences, USA 106, 73–78.CrossRefGoogle ScholarPubMed
Hyeon, C. & Onuchic, J. N. (2007). Mechanical control of the directional stepping dynamics of the kinesin motor. Proceedings of the National Academy of Sciences, USA 104, 17382–17387.CrossRefGoogle ScholarPubMed
Hyeon, C. & Thirumalai, D. (2003). Can energy landscape roughness of proteins and RNA be measured by using mechanical unfolding experiments? Proceedings of the National Academy of Sciences, USA 100, 10249–10253.CrossRefGoogle ScholarPubMed
Hyeon, C., Jennings, P. A., Adams, J. A. & Onuchic, J. N. (2009). Ligand-induced global transitions in the catalytic domain of protein kinase A. Proceedings of the National Academy of Sciences, USA 106, 3023–3028.CrossRefGoogle ScholarPubMed
Igumenova, T. I., Lee, A. L. & Wand, A. J. (2005). Backbone and side chain dynamics of mutant calmodulin-peptide complexes. Biochemistry 44, 12627–12639.Google Scholar
Karplus, M. & McCammon, J. A. (1981). The internal dynamics of globular proteins. CRC Critical Reviews in Biochemistry and Molecular Biology 9, 293–349.Google ScholarPubMed
Karplus, M. & McCammon, J. A. (1983). Dynamics of proteins: elements and function. Annual Review of Biochemistry 52, 263–300.Google Scholar
Kauzmann, W. (1959). Some factors in the interpretation of protein denaturation. Advances in Protein Chemistry 14, 1–63.Google Scholar
Kaya, H. & Chan, H. S. (2003). Solvation effects and driving forces for protein thermodynamic and kinetic cooperativity: how adequate is native-centric topological modeling? Journal of Molecular Biology 326, 911–931.Google Scholar
Kern, D. & Zuiderweg, E. R. P. (2003). The role of dynamics in allosteric regulation. Current Opinion in Structural Biology 13, 748–757.Google Scholar
Kern, D., Eisenmesser, E. Z. & Wolf-Watz, M. (2005). Enzyme dynamics during catalysis measured by NMR spectroscopy. Methods in Enzymology 394, 507–524.CrossRefGoogle ScholarPubMed
Khalili, M. & Wales, D. (2008). Pathways for conformational change in nitrogen regulatory protein c from discrete path sampling. Journal of Physical Chemistry B 112, 2456–2465.Google Scholar
Kim, Y. B., Kalinowski, S. S. & Marcinkeviciene, J. (2007). A pre-steady state analysis of ligand binding to human glucokinase: evidence for a preexisting equilibrium. Biochemistry 46, 1423–1431.CrossRefGoogle ScholarPubMed
Kondrashov, D. A., Cui, Q. & Phillips, G. N. Jr (2006). Optimization and evaluation of a coarse-grained model of protein motion using X-ray crystal data. Biophysical Journal 91, 2760–2767.Google Scholar
Koshland, D. E., Nemethy, G. & Filmer, D. (1966). Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5, 365–385.CrossRefGoogle ScholarPubMed
Krivov, S. & Karplus, M. (2002). Free energy disconnectivity graphs: application to peptide models. Journal of Chemical Physics 117, 10894–10903.CrossRefGoogle Scholar
Krivov, S. V. & Karplus, M. (2004). Hidden complexity of free energy surfaces for peptide (protein) folding. Proceedings of the National Academy of Sciences, USA 101, 14766–14770.CrossRefGoogle ScholarPubMed
Krivov, S. V., Muff, S., Caflisch, A. & Karplus, M. (2008). One-dimensional barrier-preserving free-energy projections of a beta-sheet miniprotein: new insights into the folding process. Journal of Physical Chemistry B 112, 8701–8714.Google Scholar
Kundu, S., Melton, J. S., Sorensen, D. C. & Phillips, G. N. (2002). Dynamics of proteins in crystals: comparison of experiment with simple models. Biophysical Journal 83, 723–732.CrossRefGoogle ScholarPubMed
La Nave, E., Scala, A., Starr, F., Sciortino, F. & Stanley, H. (2000). Instantaneous normal mode analysis of supercooled water. Physical Review Letters 84, 4605–4608.Google Scholar
Leitner, D. M. (2008). Energy flow in proteins. Annual Review of Physical Chemistry 59, 233–259.CrossRefGoogle ScholarPubMed
Leitner, D. M. (2009). Frequency-resolved communication maps for proteins and other nanoscale materials. Journal of Chemical Physics 130, 195101.CrossRefGoogle ScholarPubMed
Lenaerts, T., Ferkinghoff-Borg, J., Stricher, F., Serrano, L., Schymkowitz, J. W. H. & Rousseau, F. (2008). Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure. BMC Structural Biology 8, 43.CrossRefGoogle ScholarPubMed
Levy, Y., Papoian, G. A., Onuchic, J. N. & Wolynes, P. G. (2004). Energy landscape analysis of protein dimers. Israel Journal of Chemistry 44, 281–297.Google Scholar
Li, W., Zhang, J., Wang, J. & Wang, W. (2008). Metal-coupled folding of Cys2His2 zinc-finger. Journal of the American Chemical Society 130, 892–900.Google Scholar
Lockless, S. W. & Ranganathan, R. (1999). Evolutionarily conserved pathways of energetic connectivity in protein families. Science 286, 295–299.CrossRefGoogle ScholarPubMed
Lucent, D., England, J. & Pande, V. (2009). Inside the chaperonin toolbox: theoretical and computational models for chaperonin mechanism. Physical Biology 6, 015003.CrossRefGoogle ScholarPubMed
Lukin, J. A., Kontaxis, G., Simplaceanu, V., Yuan, Y., Bax, A. & Ho, C. (2003). Quaternary structure of hemoglobin in solution. Proceedings of the National Academy of Sciences, USA 100, 517–520.CrossRefGoogle ScholarPubMed
Ma, J. (2005). Usefulness and limitations of normal mode analysis in modeling dynamics of biomolecular complexes. Structure 13, 373–380.CrossRefGoogle ScholarPubMed
Maisuradze, G. G., Liwo, A. & Scheraga, H. A. (2009a). How adequate are one- and two-dimensional free energy landscapes for protein folding dynamics? Physical Review Letters 102, 238102.Google Scholar
Maisuradze, G. G., Liwo, A. & Scheraga, H. A. (2009b). Principal component analysis for protein folding dynamics. Journal of Molecular Biology 385, 312–329.Google Scholar
Malmendal, A., Evenas, J., Forsen, S. & Akke, M. (1999). Structural dynamics in the C- terminal domain of calmodulin at low calcium levels. Journal of Molecular Biology 293, 883–899.Google Scholar
Marcovitz, A. & Levy, Y. (2009). Arc-repressor dimerization on DNA: folding rate enhancement by colocalization. Biophysical Journal 96, 4212–4220.Google Scholar
Marcus, R. & Sutin, N. (1985). Electron transfers in chemistry and biology. Biochimica et Biophysica Acta 811, 265–322.Google Scholar
Marques, O. & Sanejouand, Y. H. (1995). Hinge-bending motion in citrate synthase arising from normal mode calculations. Proteins 23, 557–560.CrossRefGoogle ScholarPubMed
Martinez, K. L., Gohon, Y., Corringer, P.-J., Tribet, C., Merola, F., Changeux, J.-P. & Popot, J.-L. (2002). Allosteric transitions of Torpedo acetylcholine receptor in lipids, detergent and amphipols: molecular interactions vs. physical constraints. FEBS Letters 528, 251–256.Google Scholar
Materese, C. K., Goldmon, C. C. & Papoian, G. A. (2008). Hierarchical organization of eglin c native state dynamics is shaped by competing direct and water-mediated interactions. Proceedings of the National Academy of Sciences, USA 105, 10659–10664.Google Scholar
McCammon, J. A., Gelin, B. R. & Karplus, M. (1977). Dynamics of folded proteins. Nature 267, 585–590.Google Scholar
Miyashita, O., Onuchic, J. N. & Wolynes, P. G. (2003). Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins. Proceedings of the National Academy of Sciences, USA 100, 12570–12575.Google Scholar
Miyashita, O., Wolynes, P. G. & Onuchic, J. N. (2005). Simple energy landscape model for the kinetics of functional transitions in proteins. Journal of Physical Chemistry B 109, 1959–1969.Google Scholar
Monod, J., Wyman, J. & Changeux, J.-P. (1965). On the nature of allosteric transitions: a plausible model. Journal of Molecular Biology 12, 88–118.Google Scholar
Nelson, S. W., Iancu, C. V., Choe, J. Y., Honzatko, R. B. & Fromm, H. J. (2000). Tryptophan fluorescence reveals the conformational state of a dynamic loop in recombinant porcine fructose-1,6-bisphosphatase. Biochemistry 39, 11100–11106.Google Scholar
Niu, X., Chen, Q., Zhang, J., Shen, W., Shi, Y. & Wu, J. (2007). Interesting structural and dynamical behaviors exhibited by the AF-6 PDZ domain upon Bcr peptide binding. Biochemistry 46, 15042–15053.Google Scholar
Nurit, H., Geisbrecht, B. V., Lambris, J. & Kavraki, L. E. (2010). Multi-scale characterization of the energy landscape of proteins with application to the C3d/Efb-C complex. Proteins: Structure, Function, and Bioinformatics 78, 1004–1014.Google Scholar
Okazaki, K. & Takada, S. (2008). Dynamic energy landscape view of coupled binding and protein conformational change: induced-fit versus population-shift mechanisms. Proceedings of the National Academy of Sciences, USA 105, 11182–11187.Google Scholar
Okazaki, K., Koga, N., Takada, S., Onuchic, J. N. & Wolynes, P. G. (2006). Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations. Proceedings of the National Academy of Sciences, USA 103, 11844–11849.CrossRefGoogle ScholarPubMed
Onuchic, J. N. & Wolynes, P. G. (2004). Theory of protein folding. Current Opinion in Structural Biology 14, 70–75.Google Scholar
Onuchic, J. N., Wolynes, P. G., Luthey-Schulten, Z. & Socci, N. D. (1995). Toward an outline of the topography of a realistic protein-folding funnel. Proceedings of the National Academy of Sciences, USA 92, 3626–3630.CrossRefGoogle ScholarPubMed
Onuchic, J. N., Luthey-Schulten, Z. & Wolynes, P. G. (1997). Theory of protein folding: the energy landscape perspective. Annual Review of Physical Chemistry 48, 545–600.Google Scholar
Ota, N. & Agard, D. A. (2005). Intramolecular signaling pathways revealed by modeling anisotropic thermal diffusion. Journal of Molecular Biology 351, 345–354.CrossRefGoogle ScholarPubMed
Pande, V. S., Grosberg, A. Y. & Tanaka, T. (2000). Heteropolymer freezing and design: towards physical models of protein folding. Reviews in Modern Physics 72, 259–314.Google Scholar
Papoian, G. A. (2008). Proteins with weakly funneled energy landscapes challenge the classical structure-function paradigm. Proceedings of the National Academy of Sciences, USA 105, 14237–14238.Google Scholar
Papoian, G. A. & Wolynes, P. G. (2003). The physics and bioinformatics of binding and folding: an energy landscape perspective. Biopolymers 68, 333–349.Google Scholar
Papoian, G. A., DeGrado, W. F. & Klein, M. L. (2003a). Probing the configurational space of a metalloprotein core: an ab initio molecular dynamics study of Duo Ferro 1 binuclear Zn cofactor. Journal of American Chemical Society 125, 560–569.Google Scholar
Papoian, G. A., Ulander, J. & Wolynes, P. G. (2003b). Role of water mediated interactions in protein–protein recognition landscapes. Journal of American Chemical Society 125, 9170–9178.Google Scholar
Papoian, G. A., Ulander, J., Eastwood, M. P., Luthey-Schulten, Z. & Wolynes, P. G. (2004). Water in protein structure prediction. Proceedings of the National Academy of Sciences, USA 101, 3352–3357.CrossRefGoogle ScholarPubMed
Paschek, D., Hempel, S. & García, A. E. (2008). Computing the stability diagram of the Trp-cage miniprotein. Proceedings of the National Academy of Sciences, USA 105, 17754–17759.Google Scholar
Pervushin, K., Vamvaca, K., Vogeli, B. & Hilvert, D. (2007). Structure and dynamics of a molten globular enzyme. Nature Structural and Molecular Biology 14, 1202–1206.CrossRefGoogle ScholarPubMed
Pincus, D. L., Cho, S. S., Hyeon, C. & Thirumalai, D. (2008). Minimal models for proteins and RNA: from folding to function. Progress in Molecular and Biological Transactions 84, 203.Google Scholar
Pisliakov, A., Cao, J., Kamerlin, S. & Warshel, A. (2009). Enzyme millisecond conformational dynamics do not catalyze the chemical step. Proceedings of the National Academy of Sciences, USA 106, 17359–17364.Google Scholar
Plotkin, S. S. & Onuchic, J. N. (2002). Understanding protein folding with energy landscape theory. Part II: Quantitative aspects. Quarterly Review of Biophysics 35, 205–286.Google Scholar
Plotkin, S. S., Wang, J. & Wolynes, P. G. (1997). Statistical mechanics of a correlated energy landscape model for protein folding funnels. Journal of Chemical Physics 106, 2932–2948.CrossRefGoogle Scholar
Ptitsyn, O. B. (1996). How molten is the molten globule? Nature Structural and Molecular Biology 3, 488–490.Google Scholar
Ptitsyn, O. B., Pain, R. H., Semisotnov, G. V., Zerovnik, E. & Razgulyaev, O. I. (1990). Evidence for a molten globule state as a general intermediate in protein folding. FEBS Letters 262, 20–24.Google Scholar
Rao, F. & Caflisch, A. (2004). The protein folding network. Journal of Molecular Biology 342, 299–306.Google Scholar
Riccardi, D., Cui, Q. & Phillips, G. N. Jr (2009). Application of elastic network models to proteins in the crystalline state. Biophysical Journal 96, 464–475.Google Scholar
Roca, M., Messer, B., Hilvert, D. & Warshel, A. (2008). On the relationship between folding and chemical landscapes in enzyme catalysis. Proceedings of the National Academy of Sciences, USA 105, 13877–13882.CrossRefGoogle ScholarPubMed
Samuni, U., Dantsker, D., Roche, C. J. & Friedman, J. M. (2007). Ligand recombination and a hierarchy of solvent slaved dynamics: the origin of kinetic phases in hemeproteins. Gene 398, 234–248.CrossRefGoogle Scholar
Scheraga, H. A., Khalili, M. & Liwo, A. (2007). Protein-folding dynamics: overview of molecular simulation techniques. Annual Reviews in Physical Chemistry 58, 57–83.Google Scholar
Schmitz, M. & Tavan, P. (2004). Vibrational spectra from atomic fluctuations in dynamics simulations. I. Theory, limitations, and a sample application. Journal of Chemical Physics 121, 12233–12246.Google Scholar
Schrader, T. E., Schreier, W. J., Cordes, T., Koller, F. O., Babitzki, G., Denschlag, R., Renner, C., Lweneck, M., Dong, S.-L., Moroder, L., Tavan, P. & Zinth, W. (2007). Light-triggered beta-hairpin folding and unfolding. Proceedings of the National Academy of Sciences, USA 104, 15729–15734.Google Scholar
Schulz, R., Krishnan, M., Daidone, I. & Smith, J. C. (2009). Instantaneous normal modes and the protein glass transition. Biophysical Journal 96, 476–484.Google Scholar
Shakhnovich, E. I. & Gutin, A. M. (1993). Engineering of stable and fast-folding sequences of model proteins. Proceedings of the National Academy of Sciences, USA 90, 7195–7199.Google Scholar
Sharp, K. & Skinner, J. J. (2006). Pump-probe molecular dynamics as a tool for studying protein motion and long range coupling. Proteins 65, 347–361.CrossRefGoogle ScholarPubMed
Shoemaker, B. A., Portman, J. J. & Wolynes, P. G. (2000). Speeding molecular recognition by using the folding funnel: the y-casting mechanism. Proceedings of the National Academy of Sciences, USA 97, 8868–8873.Google Scholar
Smrcka, A. V., Kichik, N., Tarrago, T., Burroughs, M., Park, M.-S., Itoga, N. K., Stern, H. A., Willardson, B. M. & Giralt, E. (2010). NMR analysis of G-protein beta gamma subunit complexes reveals a dynamic G(alpha)-G beta gamma subunit interface and multiple protein recognition modes. Proceedings of the National Academy of Sciences, USA 107, 639–644.CrossRefGoogle Scholar
Socci, N. D., Onuchic, J. N. & Wolynes, P. G. (1996). Diffusive dynamics of the reaction coordinate for protein folding funnels. Journal of Chemical Physics 104, 5860–5868.Google Scholar
Soheilifard, R., Makarov, D. E. & Rodin, G. J. (2008). Critical evaluation of simple network models of protein dynamics and their comparison with crystallographic B-factors. Physical Biology 5, 26008.Google Scholar
Suel, G., Lockless, S., Wall, M. & Ranganathan, R. (2003). Evolutionarily conserved networks of residues mediate allosteric communication in proteins. Nature Structural and Molecular Biology 10, 59–69.CrossRefGoogle ScholarPubMed
Sugase, K., Dyson, H. J. & Wright, P. E. (2007). Mechanism of coupled folding and binding of an intrinsically disordered protein. Nature 447, 1021–1025.Google Scholar
Tama, F. & Brooks, C. L. (2006). Symmetry, form, and shape: guiding principles for robustness in macromolecular machines. Annual Review of Biophysics and Biomolecular Structure 35, 115–133.Google Scholar
Tama, F. & Sanejouand, Y. H. (2001). Conformational change of proteins arising from normal mode calculations. Protein Engineering 14, 1–6.Google Scholar
Tang, C., Louis, J. M., Aniana, A., Suh, J.-Y. & Clore, G. M. (2008). Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease. Nature 455, 693–696.Google Scholar
Tang, S., Liao, J.-C., Dunn, A. R., Altman, R. B., Spudich, J. A. & Schmidt, J. P. (2007). Predicting allosteric communication in myosin via a pathway of conserved residues. Journal of Molecular Biology 373, 1361–1373.Google Scholar
Tehver, R., Chen, J. & Thirumalai, D. (2009). Allostery wiring diagrams in the transitions that drive the GroEL reaction cycle. Journal of Molecular Biology 387, 390–406.Google Scholar
Thielges, M. C., Zimmermann, J., Yu, W., Oda, M. & Romesberg, F. E. (2008). Exploring the energy landscape of antibody-antigen complexes: protein dynamics, flexibility, and molecular recognition. Biochemistry 47, 7237–7247.Google Scholar
Tsai, C.-J., Sol, A. D. & Nussinov, R. (2009). Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms. Molecular Biosystems 5, 207–216.Google Scholar
Turjanski, A. G., Gutkind, J. S., Best, R. B. & Hummer, G. (2008). Binding-induced folding of a natively unstructured transcription factor. PLoS Computational Biology 4, e1000060.Google Scholar
van der Vaart, A., Bursulaya, B. D., Brooks, C. L. & Merz, K. M. (2000). Are many-body effects important in protein folding? Journal of Physical Chemistry B 104, 9554–9563.Google Scholar
Volkman, B. F., Lipson, D., Wemmer, D. E. & Kern, D. (2001). Two-state allosteric behavior in a single-domain signaling protein. Science 291, 2429–2433.Google Scholar
Wang, J., Zhang, K., Lu, H. & Wang, E. (2005). Quantifying kinetic paths of protein folding. Biophysical Journal 89, 1612–1620.Google Scholar
Wang, J., Zhang, K., Lu, H. & Wang, E. (2006). Dominant kinetic paths on biomolecular binding-folding energy landscape. Physical Review Letters 96, 168101.Google Scholar
Whitford, P. C., Miyashita, O., Levy, Y. & Onuchic, J. N. (2007). Conformational transitions of adenylate kinase: switching by cracking. Journal of Molecular Biology 366, 1661–1671.CrossRefGoogle ScholarPubMed
Whitford, P. C., Gosavi, S. & Onuchic, J. N. (2008a). Conformational transitions in adenylate kinase – allosteric communication reduces misligation. Journal of Biological Chemistry 283, 2042–2048.Google Scholar
Whitford, P., Onuchic, J. N. & Wolynes, P. G. (2008b). Energy landscape along an enzymatic reaction trajectory: hinges or cracks? HFSP Journal 2, 61–64.Google Scholar
Wu, S., Zhuravlev, P. I. & Papoian, G. A. (2008). High resolution approach to the native state ensemble kinetics and thermodynamics. Biophysical Journal 95, 5524–5532.Google Scholar
Xu, C., Tobi, D. & Bahar, I. (2003). Allosteric changes in protein structure computed by a simple mechanical model: hemoglobin T↔R2 transition. Journal of Molecular Biology 333, 153–168.Google Scholar
Xu, Y., Colletier, J. P., Jiang, H., Silman, I., Sussman, J. L. & Weik, M. (2008). Induced-fit or preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design. Protein Science 17, 601–605.Google Scholar
Yang, L.-W., Eyal, E., Chennubhotla, C., Jee, J., Gronenborn, A. M. & Bahar, I. (2007). Insights into equilibrium dynamics of proteins from comparison of NMR and X-ray data with computational predictions. Structure 15, 741–749.Google Scholar
Youn, H., Koh, J. & Roberts, G. P. (2008). Two-state allosteric modeling suggests protein equilibrium as an integral component for cyclic AMP (cAMP) speci_city in the cAMP receptor protein of Escherichia coli. Journal of Bacteriology 190, 4532–4540.Google Scholar
Yue, K. & Dill, K. A. (1995). Forces of tertiary structural organization in globular proteins. Proceedings of the National Academy of Sciences, USA 92, 146–150.Google Scholar
Zheng, W. (2008). A unification of the elastic network model and the Gaussian network model for optimal description of protein conformational motions and fluctuations. Biophysics Journal 94, 3853–3857.Google Scholar
Zheng, W., Brooks, B., Doniach, S. & Thirumalai, D. (2005). Network of dynamically important residues in the open/closed transition in polymerases is strongly conserved. Structure 13, 565–577.Google Scholar
Zhuravlev, P. I., Materese, C. K. & Papoian, G. A. (2009). Deconstructing the native state: energy landscapes, function, and dynamics of globular proteins. Journal of Physical Chemistry B 113, 8800–8812.Google Scholar
Zhuravleva, A., Korzhnev, D. M., Nolde, S. B., Kay, L. E., Arseniev, A. S., Billeter, M. & Orekhov, V. Y. (2007). Propagation of dynamic changes in barnase upon binding of barstar: an NMR and computational study. Journal of Molecular Biology 367, 1079–1092.CrossRefGoogle ScholarPubMed
Zong, C., Papoian, G. A., Ulander, J. & Wolynes, P. G. (2006). Role of topology, nonadditivity, and water-mediated interactions in predicting the structures of alpha/beta proteins. Journal of American Chemical Society 128, 5168–5176.Google Scholar
Zwanzig, R. (2001). Nonequilibrium Statistical Mechanics. Oxford: Oxford University Press.Google Scholar