Studying protein-polymer complexes at the molecular level is crucial for understanding how polymers interact with proteins and affect their stability and function. The complexation process of lysozyme (LYZ) and poly-(acrylic acid) (PAA) is highly dependent on pH and temperature, influencing both the stability and binding dynamics of the interaction network. Using atomistic molecular dynamics simulations, we explored how these environmental factors shape the binding strength, molecular rearrangements, and conformational adaptability of the LYZ-PAA complexes. The results reveal that pH has a pronounced effect on the resulting complexes, where higher pH disrupts protein-polymer interactions due to increased electrostatic repulsion. At the same time, an increase in temperature leads to more transient and fluctuating interactions while maintaining overall binding stability. Structural analysis further supports these trends, showing that higher temperatures promote flexibility, while higher pH leads to greater conformational expansion and reduced stability. Through association rate calculations and hydrogen bonding analysis, we identified key residues, such as arginine and lysine, that dominate the LYZ/PAA interaction at lower pH levels, while higher pH values promote a shift toward hydrophobic interactions. Our findings highlight the critical role of pH and temperature in controlling molecular interactions, offering valuable insights for applications in biomaterials and protein-based delivery systems.
Ektirici et al. (Thu,) studied this question.