Anisotropic Interactions in Protein Mixtures: Self Assembly and Phase Behavior in Aqueous Solution

Area of Science:

• Biophysics
• Computational Biology
• Protein Chemistry

Background:

• Proteins can self-assemble into stable structures in aqueous solutions.
• Electrostatic interactions are key drivers of protein self-assembly.

Purpose of the Study:

• Investigate the role of anisotropic electrostatic interactions in protein phase separation.
• Understand the self-assembly mechanisms of lysozyme/α-lactalbumin mixtures.

Main Methods:

• Parallel tempering Monte Carlo simulations.
• Studied protein phase separation in lysozyme/α-lactalbumin mixtures.
• Analyzed protein alignment and its dependence on electrostatic anisotropy.

Main Results:

• Anisotropic electrostatic interactions are critical for driving protein self-assembly.
• Proteins align strongly with their charge distribution in both dilute and concentrated phases.
• Phase separation is suppressed when electrostatic anisotropy is neglected, even with mutations.

Conclusions:

• Subtle electrostatic interactions play a significant role in protein self-assembly.
• Protein alignment is essential for phase separation in crowded biomolecular environments.
• Findings challenge the dominance of short-ranged forces in such systems.