Quantitative theory of the globule-to-coil transition. 1. Link density distribution in a globule and its radius of gyration

Grosberg, Alexander Y.; Кузнецов, Д. В.

doi:10.1021/ma00033a022

Cited by 171 publications

(165 citation statements)

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“…15 In the past, the continuous collapse of polymers has been successfully treated by mean-field theories [16][17][18][19] that relate the free energy of the chain to its density. Since the first theoretical description of homopolymer collapse by Flory, 16 coil-to-globule theories have been developed that describe the expanded coil in good solvent as well as the compact globule in poor solvent.…”

Section: Introductionmentioning

confidence: 99%

“…Since the first theoretical description of homopolymer collapse by Flory, 16 coil-to-globule theories have been developed that describe the expanded coil in good solvent as well as the compact globule in poor solvent. [18][19][20][21] Experimentally, the observation of unfolded proteins over a broad range of solvent conditions by means of single-molecule Förster resonance energy transfer (FRET) allowed the quantitative application of these a) Authors to whom correspondence should be addressed. Electronic addresses: h.hofmann@bioc.uzh.ch and schuler@bioc.uzh.ch.…”

Section: Introductionmentioning

confidence: 99%

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Single-molecule spectroscopy of the unexpected collapse of an unfolded protein at low pH

Hofmann

Nettels

Schuler

2013

The Journal of Chemical Physics

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The dimensions of intrinsically disordered and unfolded proteins critically depend on the solution conditions, such as temperature, pH, ionic strength, and osmolyte or denarurant concentration. However, a quantitative understanding of how the complex combination of chain-chain and chain-solvent interactions is affected by the solvent is still missing. Here, we take a step towards this goal by investigating the combined effect of pH and denaturants on the dimensions of an unfolded protein. We use single-molecule fluorescence spectroscopy to extract the dimensions of unfolded cold shock protein (CspTm) in mixtures of the denaturants urea and guanidinium chloride (GdmCl) at neutral and acidic pH. Surprisingly, even though a change in pH from 7 to 2.9 increases the net charge of CspTm from -3.8 to +10.2, the radius of gyration of the chain is very similar under both conditions, indicating that protonation of acidic side chains at low pH results in additional hydrophobic interactions. We use a simple shared binding site model that describes the joint effect of urea and GdmCl, together with polyampholyte theory and an ion cloud model that includes the chemical free energy of counterion interactions and side chain protonation, to quantify this effect. The dimensions of intrinsically disordered and unfolded proteins critically depend on the solution conditions, such as temperature, pH, ionic strength, and osmolyte or denarurant concentration. However, a quantitative understanding of how the complex combination of chain-chain and chain-solvent interactions is affected by the solvent is still missing. Here, we take a step towards this goal by investigating the combined effect of pH and denaturants on the dimensions of an unfolded protein. We use single-molecule fluorescence spectroscopy to extract the dimensions of unfolded cold shock protein (CspTm) in mixtures of the denaturants urea and guanidinium chloride (GdmCl) at neutral and acidic pH. Surprisingly, even though a change in pH from 7 to 2.9 increases the net charge of CspTm from −3.8 to +10.2, the radius of gyration of the chain is very similar under both conditions, indicating that protonation of acidic side chains at low pH results in additional hydrophobic interactions. We use a simple shared binding site model that describes the joint effect of urea and GdmCl, together with polyampholyte theory and an ion cloud model that includes the chemical free energy of counterion interactions and side chain protonation, to quantify this effect. © 2013 AIP Publishing LLC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single-molecule spectroscopy of the unexpected collapse of an unfolded protein at low pH

Hofmann

Nettels

Schuler

2013

The Journal of Chemical Physics

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“…In this review, we focus on a description of the concepts borrowed directly from polymer physics [20][21][22][23][24][25][26][27][28] that provide the necessary framework for understanding the driving forces and mechanisms for protein aggregation. In our parlance, protein aggregation refers is allencompassing because we do not distinguish between ordered versus amorphous aggregates.…”

Section: Introductionmentioning

confidence: 99%

A polymer physics perspective on driving forces and mechanisms for protein aggregation

Pappu

Wang

Vitalis

et al. 2008

Archives of Biochemistry and Biophysics

154

172

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Protein aggregation is a commonly occurring problem in biology. Cells have evolved stress-response mechanisms to cope with problems posed by protein aggregation. Yet, these quality control mechanisms are overwhelmed by chronic aggregation-related stress and the resultant consequences of aggregation become toxic to cells. As a result, a variety of systemic and neurodegenerative diseases are associated with various aspects of protein aggregation and rational approaches to either inhibit aggregation or manipulate the pathways to aggregation might lead to an alleviation of disease phenotypes. To develop such approaches, one needs a rigorous and quantitative understanding of protein aggregation. Much work has been done in this area. However, several unanswered questions linger, and these pertain primarily to the actual mechanism of aggregation as well as to the types of intermolecular associations and intramolecular fluctuations realized at low protein concentrations. It has been suggested that the concepts underlying protein aggregation are similar to those used to describe the aggregation of synthetic polymers. Following this suggestion, the relevant concepts of polymer aggregation are introduced. The focus is on explaining the driving forces for polymer aggregation and how these driving forces vary with chain length and solution conditions. It is widely accepted that protein aggregation is a nucleation-dependent process. This view is based mainly on the presence of long times for the accumulation of aggregates and the elimination of these lag times with "seeds". In this sense, protein aggregation is viewed as being analogous to the aggregation of colloidal particles. The theories for polymer aggregation reviewed in this work suggest an alternative mechanism for the origin of long lag times in protein aggregation. The proposed mechanism derives from the recognition that polymers have unique dynamics that distinguish them from other aggregation-prone systems such as colloidal particles.

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“…For C, we use the approach proposed by Grosberg and Kuznetsov (1992) for the elastic free energy change in polymers, which establishes C as proportional to a function of the expansion factor d of the form C / ðd À2 þ d 2 Þ. The advantage of this form is that the expansion factor can take values smaller than unity, which allows the capture of any potential volume-based transitions or contractions.…”

Section: Helmholtz Free Energy Expressionsmentioning

confidence: 99%

Molecular thermodynamics modeling of equilibrium moisture in foods

Vásquez

Braganza

Coronella

2011

Journal of Food Engineering

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Quantitative theory of the globule-to-coil transition. 1. Link density distribution in a globule and its radius of gyration

Cited by 171 publications

References 11 publications

Single-molecule spectroscopy of the unexpected collapse of an unfolded protein at low pH

Single-molecule spectroscopy of the unexpected collapse of an unfolded protein at low pH

A polymer physics perspective on driving forces and mechanisms for protein aggregation

Molecular thermodynamics modeling of equilibrium moisture in foods

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