Low-density/high-density liquid phase transition for model globular proteins.

Area of Science:

• Physical Chemistry
• Computational Biophysics
• Soft Matter Physics

Background:

• Understanding protein behavior in solution is crucial for biophysics and materials science.
• Macromolecular interactions influence phase transitions and nucleation phenomena.
• Existing models often simplify the complex interactions of globular proteins.

Purpose of the Study:

• To investigate how molecule size (excluded volume) and interaction range affect protein surface tension, phase diagrams, and nucleation.
• To explore the applicability of a parametrized potential bridging Lennard-Jones and ten Wolde-Frenkel models for globular proteins.
• To analyze homogeneous nucleation pathways, barriers, and rates using classical density functional theory (DFT).

Main Methods:

• Monte Carlo simulations were employed to model protein interactions.
• Finite temperature classical density functional theory (DFT) was utilized for nucleation studies.
• A parametrized potential was developed to smoothly transition between simple fluid and protein interaction models.

Main Results:

• Large excluded volume, characteristic of proteins, dominates liquid-vapor surface tension and nucleation.
• Interaction range significantly impacts nucleation only for small excluded volumes (simple fluids).
• Homogeneous nucleation barriers are low (few kBT), and rates are higher than classical nucleation theory predicts.

Conclusions:

• Excluded volume is the primary factor governing protein phase behavior and nucleation.
• Classical nucleation theory may underestimate nucleation rates for globular proteins.
• The study provides insights into protein self-assembly and phase transitions.