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目的研究单克隆抗体依那西普融合蛋白二聚体在不同状态下的动力学稳定性和热力学稳定性,为其活性保护的研究奠定基础。方法利用Gromacs 4.6分子模拟软件和Amber99sb-ildn分子力场以及拉伸模拟和伞状采样的方法,获取依那西普抗体蛋白的解离自由能和解离拉力的变化。结果研究结果表明,依那西普抗体蛋白在真空中的解离自由能是在水溶液中的10.05倍,其在真空中解离的平均作用力是在水溶液中的3.03倍。溶剂化环境对于抗体蛋白的稳定性具有显著的影响,而真空冷冻干燥可以提高其结构的稳定性。结论拉伸模拟过程中,最大拉力简单易得,且影响因素少,可以用最大拉力表征抗体蛋白二聚体的活性结构稳定性。
Objective To study the kinetic and thermodynamic stability of the monoclonal antibody etanercept fusion protein dimer under different conditions and lay the foundation for the study of its activity protection. Methods The dissociative free energy and dissociation tensions of etanercept antibody were determined by using Gromacs 4.6 molecular modeling software and Amber99sb-ildn molecular force field as well as tensile simulation and umbrella sampling. Results The results showed that the free energy of dissociation of etanercept antibody in vacuum was 10.05 times of that in aqueous solution and the average force of dissociation in vacuum was 3.03 times of that in aqueous solution. Solvated environment has a significant impact on the stability of antibody proteins, while vacuum freeze-drying can improve its structural stability. Conclusion In the process of tensile simulation, the maximum tensile force is simple and easy to obtain, and the influencing factors are few. The maximum tensile force can be used to characterize the active structural stability of the antibody protein dimer.