Published Online: 15 DEC 2009
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Pace, C. N., Grimsley, G. R. and Scholtz, J. M. 2009. Protein Stability. eLS. .
- Published Online: 15 DEC 2009
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Proteins must fold to a globular conformation to carry out the most important tasks in living organisms. The folded, biologically active conformation of a protein is only marginally more stable than unfolded, inactive conformations, thus making proteins more stable is important in medicine and basic research. The major destabilizing force that must be overcome is conformational entropy. The major stabilizing forces are the hydrophobic effect and hydrogen bonding. The ionizable side-chains of amino acid residues may also contribute favourably to protein stability through attractive charge–charge interactions, ion pair formation, or the formation of hydrogen bonds when such groups are buried in the protein interior.
Under physiological conditions, a folded protein is ≈20 to 60 kJmol–1 more stable than unfolded forms.
The major destabilizing force to protein folding is conformational entropy, which contributes ≈7 kJ mol−1 per residue.
The major stabilizing forces are the hydrophobic effect, where the burying of each –CH2– contributes ≈−5 kJ mol−1, and hydrogen bonding, especially buried intramolecular hydrogen bonds, which may contribute ≈−7 kJ mol−1 per bond.
The ionizable side-chains of amino acid residues may contribute favourably to protein stability through attractive charge–charge interactions, ion pair formation and hydrogen bonding when the ionizable group is buried in the protein interior.
- protein stability;
- conformational entropy;
- hydrophobic effect;
- hydrogen bonding;
- protein ionizable groups;