Bioactive structural stability of insulin in hydrated ionic liquids

doi:10.11949/j.issn.0438-1157.20161499

Abstract

Abstract:

Ionic liquids, which have unique, modulated molecular structure and excellent physicochemical properties, are applied to study the structural stability of protein. In the present study, insulin was selected as a heat sensitive protein medicine in order to investigate the bioactive structural stability of protein in ionic liquids with different mass fractions of water by using molecular dynamics simulation and microcalorimetry. In order to analyze thoroughly the relationship between the content of water molecules and the protein stability, the interaction energy between the ionic liquids and the insulin was calculated. Finally, the experimental results show that the thermal denaturation temperature of insulin is more than 68℃ when the mass fraction of water is less than 25.00%. Moreover, in the hydrated ionic liquids at the water content as 25.00%, a large number of cations and anions are adsorbed on the surface of insulin owing on the strong electrostatic interaction between the insulin and the ions, which reveals the stabilizing effect of hydrated ionic liquids. Generally, macroscopic experimental study and microscopic dynamics calculation, as attempted by this research, provide a new analytical method to interpret the stabilization mechanism of ionic liquids with different water content for protein.

Key words: ionic liquids, insulin, mass fraction of water, stability of protein, molecular simulation, microcalorimetry

摘要：

离子液体以其独特的、可修饰的分子结构以及优良的物理化学性质被应用于蛋白质的稳定性研究。采用分子动力学模拟方法及微量热法，研究热敏性蛋白药物胰岛素在不同水质量分数下水合离子液体中活性结构的稳定性，并深入分析离子液体与胰岛素之间的相互作用及水分子与蛋白质稳定性之间的关系。研究结果表明，当水质量分数低于25.00%时，胰岛蛋白的热变性温度能保持在68℃以上。且通过模拟分析得出，含水量25.00%的水合离子液体体系中，大量阴、阳离子在胰岛蛋白表面聚集，并通过较强的静电相互作用吸附在其表面，从而对蛋白质的活性结构展现出良好的稳定效果。结合宏观实验研究及微观动力学计算阐释了不同水含量的离子液体稳定蛋白质的作用机理，并为离子液体对蛋白质的稳定作用研究提供了一种新的分析方法。

关键词: 离子液体, 胰岛素, 水质量分数, 蛋白质稳定性, 分子模拟, 微量热法

CLC Number:

O6-39

PAN Xiaoli, LI Daixi, WEI Dongqing. Bioactive structural stability of insulin in hydrated ionic liquids[J]. CIESC Journal, 2017, 68(5): 2035-2041.

潘晓莉, 李代禧, 魏冬青. 胰岛素活性结构在水合离子液体中的稳定性[J]. 化工学报, 2017, 68(5): 2035-2041.

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