Protein stability and dynamics in the pressure-temperature plane

Area of Science:

• Biophysics
• Protein Chemistry
• Materials Science

Background:

• Proteins exhibit complex pressure-temperature (P-T) stability diagrams.
• The elliptical shape of these diagrams is based on specific assumptions.
• Protein aggregation and fibril formation represent important extensions to basic stability models.

Purpose of the Study:

• To discuss the P-T stability diagram of proteins and its underlying assumptions.
• To explore extensions of the P-T diagram, including aggregation and fibril formation.
• To investigate the molecular origins of protein stability, focusing on partial molar volume, cavities, and hydration.

Main Methods:

• Analysis of existing data on protein P-T stability.
• Theoretical modeling of partial molar volume, considering cavities and hydration.
• Examination of changes in thermal expansivity, compressibility, and heat capacity during unfolding.
• Consideration of experimental observations on fibril stability.

Main Results:

• Mature protein fibrils demonstrate remarkable stability under extreme pressure conditions.
• The molecular origins of protein stability are linked to protein volume, cavities, and hydration.
• Changes in thermodynamic parameters (expansivity, compressibility, heat capacity) relate to unfolding enthalpy and volume fluctuations.

Conclusions:

• The study of water-soluble polymers may enhance understanding of protein stability diagrams.
• While water's role in protein behavior is established, the significance of cavities requires further investigation.
• Protein P-T stability is influenced by molecular-level factors like cavities and hydration.