Forces contributing to the conformational stability of proteins

  title={Forces contributing to the conformational stability of proteins},
  author={C. Nick Pace and Bret A. Shirley and Marsha McNutt and Ketan S. Gajiwala},
  journal={The FASEB Journal},
  pages={75 - 83}
For 35 years, the prevailing view has been that the hydrophobic effect is the dominant force in protein folding. The importance of hydrogen bonding was always clear, but whether it made a net favorable contribution to protein stability was not. Studies of mutant proteins have improved our understanding of the forces stabilizing proteins. They suggest that hydrogen bonding and the hydrophobic effect make large but comparable contributions to the stability of globular proteins.—Pace, C. N… 

Forces stabilizing proteins

The Physics of the Interactions Governing Folding and Association of Proteins

Abstract: The review discusses the molecular origins of the forces and free energies that determine several things about proteins, and how experiment and theory reveal this information. The first

Lessons about Protein Stability from in vitro Selections

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  • Biology
    Chembiochem : a European journal of chemical biology
  • 2011
All the types of interactions that are known to be beneficial for protein stability are slightly better optimized in those proteins, which indicated that possibly an upper limit does not exist for protein conformational stability.

Contribution of hydrophobic interactions to protein stability.


The results suggest that proline mutations generally increase protein stability, and the stabilizing mechanism of the hydrophobic effect appears to be similar for both proteins.

On hydrophobicity and conformational specificity in proteins.

Studying the role of cooperative hydration in stabilizing folded protein states

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  • Biology
    Journal of structural biology
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The present review aims to provide a reassessment of the factors important for folding in light of current knowledge, including contributions to the free energy of folding arising from electrostatics, hydrogen-bonding and van der Waals interactions, intrinsic propensities, and hydrophobic interactions.

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It is estimated that hydrogen bonding contributes about 110 kcal/mol to the conformational stability of RNase T1 and that this is comparable to the contribution of the hydrophobic effect, in good agreement with results from several related systems.

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  • Biology
    Methods in enzymology
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Studies on protein stability with T4 lysozyme.

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  • Biology, Chemistry
    Protein science : a publication of the Protein Society
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A thermodynamic argument is presented to show that the variation is mainly due to that in the flexibility of the protein molecule at the site of mutation, and that the maximum destabilization occurs when the protein at the sites of mutation is rigid, in which case the value of the destabilization is approximately given by the work of cavity formation in water.

Energetics of repacking a protein interior.

To test whether interactions in the hydrophobic core of a protein can be adequately modeled based on the properties of a liquid hydrocarbon, we measured the unfolding free energies of the wild-type

Hydration effects in protein unfolding.

Coupling of local folding to site-specific binding of proteins to DNA.

Estimates of the number of residues that fold on binding obtained from this analysis agree with structural data, and structural comparisons indicate that these local folding transitions create key parts of the protein-DNA interface.