中国物理B ›› 2025, Vol. 34 ›› Issue (8): 88701-088701.doi: 10.1088/1674-1056/add50b

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Molecular simulation study on phase separation of immunoglobulin G

Lv-Meng Hu(胡吕梦)1, Yuan-Qiang Chen(陈远强)1, Hong-Ming Ding(丁泓铭)1,†, and Yu-Qiang Ma(马余强)2,3   

  1. 1 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China;
    2 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China;
    3 Jiangsu Physical Science Research Center, Nanjing 210093, China
  • 收稿日期:2025-04-02 修回日期:2025-04-28 接受日期:2025-05-07 出版日期:2025-07-17 发布日期:2025-07-21
  • 通讯作者: Hong-Ming Ding E-mail:dinghm@suda.edu.cn
  • 基金资助:
    Project supported by the National Natural Science Foundation of China (Grant Nos. 12222506, 12347102, and 12174184).

Molecular simulation study on phase separation of immunoglobulin G

Lv-Meng Hu(胡吕梦)1, Yuan-Qiang Chen(陈远强)1, Hong-Ming Ding(丁泓铭)1,†, and Yu-Qiang Ma(马余强)2,3   

  1. 1 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China;
    2 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China;
    3 Jiangsu Physical Science Research Center, Nanjing 210093, China
  • Received:2025-04-02 Revised:2025-04-28 Accepted:2025-05-07 Online:2025-07-17 Published:2025-07-21
  • Contact: Hong-Ming Ding E-mail:dinghm@suda.edu.cn
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Grant Nos. 12222506, 12347102, and 12174184).

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摘要： 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.

关键词: phase separation, immunoglobulin G, coarse-graining, molecular dynamics

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.

Key words: phase separation, immunoglobulin G, coarse-graining, molecular dynamics

中图分类号:  (Molecular dynamics simulation)

  • 87.10.Tf
64.75.-g (Phase equilibria) 87.15.-v (Biomolecules: structure and physical properties) 87.15.A- (Theory, modeling, and computer simulation)