Electrostatic unfolding and interactions of albumin driven by pH changes: a molecular dynamics study

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Protein aggregation is crucial for understanding misfolded protein disorders and developing biomaterials.
• Albumin is a well-studied model protein, but its aggregation behavior under various conditions requires further investigation.

Purpose of the Study:

• To investigate how electrostatic interactions influence the conformation of a single albumin molecule before self-assembly.
• To analyze albumin's tertiary structure and solvent-accessible surface area following electrostatically induced partial denaturation.

Main Methods:

• All-atom molecular dynamics simulations of albumin.
• Analysis of tertiary structure and solvent accessible surface area.
• Investigation of inter-protein electrostatic interactions.

Main Results:

• Electrostatic interactions significantly affect albumin's conformation prior to self-assembly.
• Partial denaturation exposes new surface areas and alters tertiary structure.
• Hydrophobic attractions and counterion binding can overcome electrostatic repulsion between charged albumin monomers.

Conclusions:

• This study enhances understanding of protein aggregation mechanisms, particularly the role of electrostatics and free ions.
• Provides insights into albumin's equilibrium conformation in a partially denatured state at low pH.
• Findings may advance the development of biocompatible protein hydrogels via electrostatic denaturation.