Zeta Potential Prediction from Protein Structure in General Aqueous Electrolyte Solutions

Area of Science:

• Biochemistry
• Physical Chemistry
• Computational Biology

Background:

• The zeta potential (ζ) governs electrostatic interactions and molecular behavior in solution.
• Understanding and predicting ζ potential is crucial for protein stability and preventing aggregation.

Purpose of the Study:

• To introduce ZPRED, a computational protocol for calculating ζ potential from protein structures.
• To validate the ZPRED model against experimental electrophoretic mobility data.

Main Methods:

• Development of the ZPRED computational protocol incorporating protein and solution properties.
• Utilizing electrokinetic models to address complexities in protein electrophoresis.
• Experimental validation using benchtop light scattering to measure electrophoretic mobilities.

Main Results:

• ZPRED accurately computes ζ potential for proteins across various solution conditions.
• Computed electrophoretic mobilities closely match experimental observations.
• The model effectively accounts for protein and solution complexities.

Conclusions:

• ZPRED provides a reliable method for predicting ζ potential and optimizing conditions to enhance protein stability.
• This tool aids in preventing aggregation, crucial for engineered biologics and industrial protein catalysts.