Analytical model for studying how environmental factors influence protein conformational stability in solution

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• Understanding protein conformational stability is crucial for biological function and therapeutic development.
• Existing models often simplify complex protein-protein interactions and environmental factors.

Purpose of the Study:

• To develop an analytical modeling strategy for predicting globular protein stability in aqueous solutions.
• To investigate the influence of temperature, pressure, and protein concentration on protein stability.

Main Methods:

• Utilized heteropolymer collapse theory incorporating temperature- and pressure-dependent hydrophobic interactions.
• Integrated protein concentration effects using a molecular thermodynamic model.
• Generalized a one-dimensional binary mixture model for protein folding.

Main Results:

• Predicted a closed-loop region of stability in the pressure-temperature plane for folded proteins.
• Demonstrated a nonmonotonic effect of protein concentration on protein stability.
• Results align with experimental and simulation data for protein solutions.

Conclusions:

• The analytical multiscale modeling approach provides a schematic but effective tool for probing protein stability.
• The model captures key thermodynamic and structural properties influencing protein behavior in solution.