Molecular simulation study on phase separation of immunoglobulin G

Abstract Understanding the liquid–liquid phase separation (LLPS) of immunoglobulin G (IgG) is crucial, as it profoundly influences IgG’s biological activity and stability. In this study, we employed coarse-grained molecular dynamics simulations to systematically investigate the phase separation behavior of IgG. We first constructed two types of IgG models: all-pair IgG model and partial-pair IgG model, and compared the coexistence curve from our simulations with experimental data. Our results showed that the partial-pair IgG model aligns better with the experimental critical temperature and critical density. Using this model, we then calculated the temperature-dependent variations of IgG’s radius of gyration, surface tension, viscosity, etc. More importantly, we demonstrated that variations in the interaction strengths among IgG molecules significantly influence their phase separation behavior. Specifically, a higher standard deviation of interaction strength at different temperatures is found to lead to more stable phase-separated states. Furthermore, we observed that the introduction of repulsive polymers and strongly attractive polymers consistently enhances IgG phase separation, while weakly attractive polymers exhibit a dual regulatory effect on the phase separation. Overall, this study provides valuable insights into the mechanisms governing IgG phase behavior, with potential implications for optimizing biopharmaceutical products.