Theory of protein folding

Onuchic, José N.; Wolynes, Peter G.

doi:10.1016/j.sbi.2004.01.009

Cited by 1,163 publications

(1,110 citation statements)

References 63 publications

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“…NIH-PA Author Manuscript NIH-PA Author Manuscript physics and the resulting "landscape" picture of protein folding have provided a new perspective for describing folding [11][12][13][14].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Repeat-protein folding: New insights into origins of cooperativity, stability, and topology

Kloss

Courtemanche

Barrick

2008

Archives of Biochemistry and Biophysics

101

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Although our understanding of globular protein folding continues to advance, the irregular tertiary structures and high cooperativity of globular proteins complicates energetic dissection. Recently, proteins with regular, repetitive tertiary structures have been identified that sidestep limitations imposed by globular protein architecture. Here we review recent studies of repeat-protein folding. These studies uniquely advance our understanding of both the energetics and kinetics of protein folding. Equilibrium studies provide detailed maps of local stabilities, access to energy landscapes, insights into cooperativity, determination of nearest-neighbor interaction parameters using statistical thermodynamics, relationships between consensus sequences and repeat-protein stability. Kinetic studies provide insight into the influence of short-range topology on folding rates, the degree to which folding proceeds by parallel (versus localized) pathways, and the factors that select among multiple potential pathways. The recent application of force spectroscopy to repeat-protein unfolding is providing a unique route to test and extend many of these findings. KeywordsRepeat-protein; Ankyrin repeat; protein folding; energy landscape; atomic force microscopy In the last twenty-five years, advances in experimental studies and in computation and theory have greatly improved our understanding of protein folding. On the experimental side, advances have come from new and improved techniques, including site-directed mutagenesis, hydrogen exchange (HX) methods, improvements to rapid mixing devices, and development of single-molecule fluorescence and force spectroscopy. Experimental advances have also come in the form of generalizations and insights from expanding databases of thermodynamic and kinetic constants for protein folding [1][2][3][4][5].On the computational side, advances in our understanding of protein folding have come from huge increases in computer speed and storage capacity, in innovative methods to study energetics of folding such as ensemble-based approaches and replica exchange methods [6,7], and distributed computing methods [8]. As with experiment, computational studies of folding, and in particular, fold prediction, have greatly benefited from expanding databases of protein structure [9,10]. On the theoretical side, the application of ideas from condensed-matter *Correspondence: barrick@jhu.edu, (410) 516-0409. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptArch Biochem Biophys. Author manuscript; available in PMC 2009 January ...

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“…NIH-PA Author Manuscript NIH-PA Author Manuscript physics and the resulting "landscape" picture of protein folding have provided a new perspective for describing folding [11][12][13][14].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Repeat-protein folding: New insights into origins of cooperativity, stability, and topology

Kloss

Courtemanche

Barrick

2008

Archives of Biochemistry and Biophysics

101

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“…Since Gō-like models lack any energetic frustration, the scope of their applications is related to the investigation of the role of geometric frustration and configurational entropy in the folding process. Their success in providing a reasonable account for kinetic properties of the folding process is related to the assumption that folding kinetics is mainly determined by native geometry, together with native state stability, and this view is indeed supported by several experimental works [11,12,13,14,15]. Along the lines indicated by the Gō-philosophy other simplified models exploiting the information present in the native state have been proposed [16,17,18,19].…”

Section: Introductionmentioning

confidence: 96%

Analysis of PIN1 WW domain through a simple statistical mechanics model

Bruscolini

Cecconi

2005

Biophysical Chemistry

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We have applied a simple statistical-mechanics Gō-like model to the analysis of the PIN1 WW domain, resorting to Mean Field and Monte Carlo techniques to characterize its thermodynamics, and comparing the results with the wealth of available experimental data. PIN1 WW domain is a 39-residues protein fragment which folds on an antiparallel β-sheet, thus representing an interesting model system to study the behavior of these secondary structure elements. Results show that the model correctly reproduces the two-state behavior of the protein, and also the trends of the experimental φT -values. Moreover, there is a good agreement between Monte Carlo results and the Mean-Field ones, which can be obtained with a substantially smaller computational effort.

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“…In addition, these complexes often contain functionally essential cofactors. Many of the principles governing the folding of small, monomeric proteins have been uncovered in recent years [1][2][3]. In contrast, much less is known about the formation of multi-protein assemblies from their unfolded monomeric constituents.…”

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Folding and assembly of hemoglobin monitored by electrospray mass spectrometry using an on-line dialysis system

Boys

Konermann

2007

J. Am. Soc. Mass Spectrom.

101

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The native structure of hemoglobin (Hb) comprises two ␣-and two ␤-subunits, each of which carries a heme group. There appear to be no previous studies that report the in vitro folding and assembly of Hb from highly unfolded ␣-and ␤-globin in a "one-pot" reaction. One difficulty that has to be overcome for studies of this kind is the tendency of Hb to aggregate during refolding. This work demonstrates that denaturation of Hb in 40% acetonitrile at pH 10.0 is reversible. A dialysis-mediated solvent change to a purely aqueous environment of pH 8.0 results in Hb refolding without any apparent aggregation. Fluorescence, Soret absorption, circular dichroism, and ESI mass spectra of the protein recorded before unfolding and after refolding are almost identical. By employing an externally pressurized dialysis cell that is coupled on-line to an ESI mass spectrometer, changes in heme binding behavior, protein conformation, and quaternary structure can be monitored as a function of time. The process occurs in a stepwise sequential manner, leading from monomeric ␣-and ␤-globin to heterodimeric species, which then assemble into tetramers. Overall, this mechanism is consistent with previous studies employing the mixing of folded ␣-and ␤-globin. However, some unexpected features are observed, e.g., a heme-deficient ␤-globin dimer that represents an off-pathway intermediate. Monomeric ␤-globin is capable of binding heme before forming a complex with an ␣-subunit. This observation suggests that holo-␣-apo-␤ globin does not represent an obligatory intermediate during Hb assembly, as had been proposed previously. The on-line dialysis/ESI-MS approach developed for this work represents a widely applicable tool for studying the folding and self-assembly of noncovalent biological complexes. (J Am Soc Mass Spectrom 2007, 18, 8 -16)

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Theory of protein folding

Cited by 1,163 publications

References 63 publications

Repeat-protein folding: New insights into origins of cooperativity, stability, and topology

Repeat-protein folding: New insights into origins of cooperativity, stability, and topology

Analysis of PIN1 WW domain through a simple statistical mechanics model

Folding and assembly of hemoglobin monitored by electrospray mass spectrometry using an on-line dialysis system

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