pH dependence of antibody/lysozyme complexation

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biophysics

Background:

• Protein-protein interactions are crucial in biological systems.
• The association of proteins is often modulated by solution conditions such as pH and ionic strength.
• Titratable residues at the interface significantly impact complex stability under varying conditions.

Purpose of the Study:

• To investigate the pH-dependent energetics of association between hen egg lysozyme and monoclonal antibodies.
• To analyze the influence of environmental factors on the titration behavior and energetics of protein-antibody complexes.
• To elucidate the role of specific factors like structural rearrangements and residue geometry in modulating complex formation.

Main Methods:

• Continuum electrostatics methods were employed to calculate pH-dependent association energetics.
• Detailed analysis of energetic contributions was performed.
• Modeled structures of mutant complexes were studied to dissect individual factor contributions.

Main Results:

• Conserved charged-residue interactions are key to association, but their energetics are significantly influenced by the local environment.
• Factors such as minor structural rearrangements, buried interfacial area, dielectric environment, and residue geometry affect titration behavior.
• Mutant complex modeling provided insights into the contribution of individual factors.

Conclusions:

• The energetics of protein-antibody association are highly sensitive to the microenvironment of titratable residues.
• Understanding these environmental influences is critical for predicting and engineering protein complex stability.
• This work highlights the interplay between intrinsic residue properties and extrinsic factors in governing protein interactions.