Skip to main content
Biology LibreTexts

Thermodynamics of Protein Stability

It is clear that proteins are not all that stable, and many contributions of varying magnitudes must sum to give the proteins marginal stability under physiological conditions.Hydrophobic interaction, defined in the new sense, must play a major role in stability. Also, since proteins are so highly packed compared to a lose denatured state, London Forces must also play a significant part. (Remember dispersion forces are short range and become most significant under conditions of closest packing.) Opposing folding is the chain conformational entropy just described. Since proteins are so marginally stable, even one unpaired buried ionic side chain, or 1-2 unpaired buried H bond donors and acceptors in the protein may be enough to "unravel" the native structure, leading to the denatured state.

Outside Links

References

  1. Bartlett, G. et al. n to pi* interactions in protein. Nature Chemical Biology. 6, pg 615 (2010).
  2. Pace, C. et al. Protein Ionizable Groups: pK values and Their Contribution to Protein Stability and Solubility. J. Biol Chem. 284, 13285 (2009)
  3. Silverstein, T. Hydrophobic Effect: J. Chem Ed. 85. 917-918 (2008)
  4. Sharp, K. & Madan, B. Hydrophobic Effect, Water Structure, and Heat Capacity Changes. J. Phys.Chem. 101, 4343 (1997)
  5. Berezovsky, I & Shakhnovich, E. Physics and Evolution of Thermophilic Adaptation. PNAS 102, 12742 (2005)
  6. Beeby et al. The genomics of disulfide bonding and protein stabilization in themophiles. PLoS Biology. 3, 1549 (2005)
  7. Courtenay, E. et al. Thermodynamics of interactions of urea and guanidinium salts with protein surfaces: relationship between solute effects on protein processes and charges in water-accessible surface area. Protein Science. 10, 2485 (2001)
  8. Korkrgian, A. et al. Computational Thermostabilzation of an Enzyme. Science. 308, pg 857 (2005)
  9. Kashefi, K. and Lovley, D. Extending the Upper Temperature Limit for Life. Science. 301, pg 934 (2003).
  10. Omta et al. Negligible Effect of Ions on the Hydrogen-bond structure in liquid water. Science, g 347, 320 (2003)
  11. Dixit et al. Molecular degregation observed in a concentrated alcohol-water solution. Nature. 416, pg 829 (2002)
  12. Pace, C.N. Polar Group Burial Contributes More to Protein Stability than Nonpolar Group Burial. Biochemistry. 40, pg 310 (2001)
  13. Water at the Nanoscale (How water enters a hydrophobic nanotube - a molecular dynamics simulation) . Nature. 294414, pg 156, 188 (2001)
  14. Shortle & Ackerman. Persistence of Native-Like Topology in a Denatured Protein in 8 M Urea. Science. 293. pg 487 (2001)
  15. Brooks et al. Taking a Walk on a Landscape (about protein foldiing) Science, 293, pg 612 (2001)
  16. Chemistry Beyond the Molecule (supramolecular chemistry). Nature. 412, pg 397 (2001)
  17. Fernandez-Lopez et al. Rings of Destruction. (Cyclic peptides as drugs). Nature. 412 pg 392, 452 (2001)
  18. Scatena et al. Water at Hydrophobic Surfaces: Weak Hydrogren Bonding and Strong Orientation Effects. Science. 292. pg 908 (2001)
  19. Maritan et al. Best Packing in Proteins and DNA. Nature, 406, pg 251, 287 (2000)
  20. Oh et al. Folding-Driven synthesis of oligomers. Nature. 414, pg 889 (2001)
  21. Molecules at the Edge (solvent interactions at interfaces) Nature. 410, pg 645 (2001)
  22. Oesterhelt et al. Unraveling a membrane protein (denaturing a protein with atomic force microscopy). Science. 288, pg 63, 143 (2000)
  23. Sohl et al. Unfolded conformations of a-lytic protease are more stable that its native state. (has large kinetic barrier to unfolding). Nature. 395, pg 817 (1998)
  24. Pascher et al. Protein folding triggered by electron transfer. Science. 271, pg 1558 (1996)
  25. Koide et al. Design of a single-layer b-sheet without a hydrophobic core. Nature. 403, pg 456 (2000)
  26. Nelson et al. Solvophobically driven folding of nonbiological oligomers. Science. 277, pg 1793 (1997)
  27. Pace,C. N. et al. Forces contributing to the conformational stability of proteins. FASEB Jouranl. 10, 75–83 (1996)