Compressibility of the protein-water interface

Area of Science:

• Biophysics
• Thermodynamics
• Computational Biology

Background:

• Protein compressibility is a key thermodynamic parameter linked to stability, flexibility, and hydrophobic interactions.
• Measuring, interpreting, and computing protein compressibility face significant technical and conceptual hurdles.

Purpose of the Study:

• To theoretically analyze protein compressibility and apply this analysis to molecular dynamics simulations.
• To decompose solution compressibility into protein and hydration shell contributions.
• To investigate the contributions of protein-water volume fluctuations and hydration shell properties to overall protein compressibility.

Main Methods:

• Theoretical analysis of protein compressibility.
• Molecular dynamics simulations of four globular proteins.
• Additively weighted Voronoi tessellation for decomposing solution compressibility.
• Analysis of protein-water volume fluctuations and hydration shell properties.

Main Results:

• Positively cross-correlated protein-water volume fluctuations contribute over half of the protein compressibility governing pressure response.
• The total protein compressibility, including cross-correlations, is approximately 45% of the bulk-water value.
• Intrinsic hydration shell compressibility is 25%-30% lower than bulk water, primarily due to proximity to the protein.

Conclusions:

• Protein compressibility is significantly influenced by protein-water interactions and hydration shell properties.
• The study provides a framework for computing protein partial compressibility, distinguishing intrinsic, hydration, and exchange contributions.
• Hydration shell compressibility is reduced near the protein surface, not due to altered water structure, but protein proximity.