The Source of Stability in Proteins

Anthony Day, PPS course participant, 1996
(October, 1996)

In this document I give an overview of protein stability. The contribution each residue makes to, or takes away from, the stability of a protein is small. Thus the stability of a protein is determined by large number of small positive and negative interaction energies. In the sections that follow I discuss some of the factors that give rise to these positive and negative interaction energies. I will also briefly discuss rates of unfolding as they relate to perceived stability (Kinetic Stability), Chemical Degradation of proteins, and the Evolution of stability.

Table of Contents

• Definition of Stability
• The Unfolded State
• The Major Factors Affecting Protein Stability
  • The Hydrophobic Effect
  • Hydrogen Bonds
  • Conformational Entropy of Unfolding
• Other Factors Affecting Protein Stability
  • Salt Bridges
  • Aromatic-Aromatic Interactions
  • Metal Binding
  • Disulphide Bonds
• Kinetic Stability
• Chemical Degradation
• Evolution and Protein Stability
• Conclusion
• References and Further Reading

Definition of Stability