A scaling relationship between thermodynamic and hydrodynamic interactions in protein solutions

Area of Science:

• Biochemistry
• Biophysics
• Protein Science

Background:

• Weak protein interactions are crucial for biological processes and biotherapeutic development.
• Understanding the molecular basis of protein self-interaction, including thermodynamic and hydrodynamic contributions, remains incomplete.
• These interactions influence protein manufacturing, stability, and therapeutic efficacy.

Purpose of the Study:

• To systematically investigate the influence of molecular attributes on protein self-interaction.
• To analyze the thermodynamic and hydrodynamic contributions to protein interaction mechanisms.
• To develop a predictive model for protein self-association and repulsion.

Main Methods:

• Evaluation of self-interaction in a diverse set of proteins exhibiting varied interaction behaviors (attractive to repulsive).
• Analysis of concentration-dependent molecular weight, diffusion coefficient, and sedimentation coefficient.
• Interconversion of interaction parameters and assessment of thermodynamic vs. hydrodynamic contributions.

Main Results:

• Demonstrated good agreement between experimental data and a hard-sphere model for weak self-association.
• Established convenient interconversions among different interaction parameters.
• Identified relationships between thermodynamic and hydrodynamic aspects of protein interactions.

Conclusions:

• Proposed an empirically derived, general scaling relationship for protein self-association and repulsion.
• Provided insights into the fundamental principles governing protein interactions.
• Offered a framework for predicting and controlling protein behavior in biological and manufacturing contexts.