Li Daixi, Liu Baolin, Guo Baisong, Liu Yaru, Zhai Zhen, Zhang Yan, Chen Chenglung, Liu Shanlin
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Institute of Lyophilization Technology, Shanghai Tofflon Science and Technology Co. Ltd., Shanghai 201108, China.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2013 Oct;30(5):936-41.
In the present research, molecular simulation and quantum chemistry calculations were combined to investigate the thermal stability of three kinds of insulin aggregations and the effect of Zn (II) ion coordination on these aggregations. The results of molecular simulation indicated that the three insulin dimers in the same sphere closed hexamer had synergistic stability. It is the synergistic stability that enhances the structural and thermal stability of insulin, preserves its bioactivity during production, storage, and delivery of insulin formulations, and prolongs its halflife in human bodies. According to the results of quantum chemistry calculations, each Zn (II)-N (Im-insulin) bond energy can reach 73.610 kJ/mol for insulin hexamer and 79.907 kJ/mol for insulin tetramer. However, the results of Gibbs free energy changes still indicats that the coordination of zinc (II) ions is unfavorable for the formation of insulin hexamer, because the standard Gibbs free energy change of the coordinate reaction of zinc (II) ions associated with the formatting insulin hexamer is positive and increased.
在本研究中，结合分子模拟和量子化学计算来研究三种胰岛素聚集体的热稳定性以及锌（II）离子配位对这些聚集体的影响。分子模拟结果表明，同一球内封闭六聚体中的三种胰岛素二聚体具有协同稳定性。正是这种协同稳定性增强了胰岛素的结构和热稳定性，在胰岛素制剂的生产、储存和递送过程中保持其生物活性，并延长其在人体中的半衰期。根据量子化学计算结果，胰岛素六聚体的每个Zn（II）-N（咪唑-胰岛素）键能可达73.610 kJ/mol，胰岛素四聚体的键能可达79.907 kJ/mol。然而，吉布斯自由能变化结果仍表明，锌（II）离子的配位不利于胰岛素六聚体的形成，因为与形成胰岛素六聚体相关的锌（II）离子配位反应的标准吉布斯自由能变化为正值且增加。
