Relationship between nonlinear pressure-induced chemical shift changes and thermodynamic parameters.

Area of Science:

• Biophysics
• Chemical Physics
• Structural Biology

Background:

• Nuclear Magnetic Resonance (NMR) chemical shift analysis probes local environmental changes in polypeptides under high hydrostatic pressure.
• Pressure dependence of chemical shifts is typically analyzed using Taylor expansions, yielding first- (B1) and second-order (B2) pressure coefficients.
• Current interpretation of B1 and B2 coefficients is often qualitative.

Purpose of the Study:

• To establish a quantitative relationship between the B2/B1 ratio and thermodynamic parameters in a two-state model.
• To apply this relationship to various peptides and proteins to understand pressure-induced conformational changes.
• To explore the physical basis of pressure-induced shifts and their implications for protein function.

Main Methods:

• Analysis of NMR chemical shift pressure dependence in the fast exchange regime.
• Application of a two-state model to relate the B2/B1 ratio to the ratio of compressibility factor differences (Δβ') and partial molar volume differences (ΔV).
• Computational simulations of water-protein interactions to model thermodynamic processes.

Main Results:

• The B2/B1 ratio is directly related to Δβ'/ΔV in a two-state model, providing thermodynamic insights.
• Average Δβ'/ΔV ratio of 1.6 GPa⁻¹ was found for random-coil model peptides under specific conditions.
• Strong correlation between amide proton and nitrogen B2/B1 values suggests a common thermodynamic origin for pressure-induced shifts.
• Experimental validation of the B2/B1 to Δβ'/ΔV relationship in β-amyloid peptide.
• HPr protein exhibits significantly more negative B2/B1 values compared to tetrapeptides, indicating distinct pressure responses.

Conclusions:

• The B2/B1 ratio offers a quantitative link to thermodynamic parameters governing pressure-induced changes in polypeptides.
• This approach provides a method to predict protein regions involved in functional interactions, as demonstrated with HPr.
• The findings advance the understanding of protein dynamics and stability under varying pressure conditions.