离子液体中胰岛素结构稳定性的分子动力学模拟

doi:10.11949/j.issn.0438-1157.20160968

化工学报 ›› 2016, Vol. 67 ›› Issue (12): 5215-5221.DOI: 10.11949/j.issn.0438-1157.20160968

离子液体中胰岛素结构稳定性的分子动力学模拟

潘晓莉¹, 李代禧¹, 魏冬青²

1 上海理工大学食品科学与工程研究所, 上海 200093;
2 上海交通大学微生物代谢国家重点实验室, 上海 200240

收稿日期:2016-07-11 修回日期:2016-08-22 出版日期:2016-12-05 发布日期:2016-12-05
通讯作者: 李代禧。dxli75@126.com
基金资助:
上海市重点学科项目（T0503，P0502）；上海市自然科学基金项目（12ZR1420400）；上海市“创新行动计划”国际科技合作项目（12430702000）；上海市联盟计划项目；上海理工大学人文社会科学基金项目（11XSY23）。

Structural stability of insulin in imidazolium ionic liquids by molecular simulation

PAN Xiaoli¹, LI Daixi¹, WEI Dongqing²

1 Institute of Food Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China;
2 State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, China

Received:2016-07-11 Revised:2016-08-22 Online:2016-12-05 Published:2016-12-05
Supported by:
supported by the Shanghai Leading Academic Discipline Project(T0503, P0502), the Natural Science Foundation of Shanghai(12ZR1420400), the "Innovation Action Plan" International Science and Technology Cooperation Project of Shanghai(12430702000), Shanghai Alliance Program and the Humanities and Social Science Fund Project of University of Shanghai for Science and Technology(11XSY23).

摘要/Abstract

摘要：

离子液体作为一种新型绿色溶剂，由于其独特的物理化学性质，被广泛应用于蛋白质的稳定性研究。选用热敏性蛋白药物胰岛素作为研究对象，采用分子动力学模拟方法，从分子层面上研究不同种类的离子液体对胰岛素结构的稳定效果。结果表明，与纯水体系相比，在常温下离子液体能够有效地稳定胰岛素的分子结构，且体系中阴离子的氢键碱性越弱，阳离子的烷基链越短，对胰岛素分子结构的稳定作用越强。并深入分析不同烷基链长度的二氰胺类离子液体与胰岛素之间的相互作用，发现相较于长烷基链离子液体，短烷基链离子液体与胰岛素之间的相互作用更强，揭示了后者能更好地维持和稳定胰岛蛋白的分子结构。

关键词: 离子液体, 胰岛素, 蛋白质稳定性, 相互作用能, 分子模拟

Abstract:

Ionic liquids, as a kind of novel green solvents, have been widely applied to structural stability study of protein due to their unique physicochemical properties. In this study, insulin was chosen as a heat-sensitive protein medicine to research the structural stability of protein in various imidazolium ionic liquids from a molecular insight by using molecular dynamics simulation. The results indicate that the ionic liquids are able to stabilize the molecular structure of insulin effectively at room temperature compared with aqueous solution. The RMSD values and the secondary structure of insulin show that the weaker the hydrogen-bond basicity of anion is, the shorter the alkyl chain of cation is, the more stable the molecular structure of insulin is. In order to explain thoroughly the effect of alkyl chain length of ionic liquid on the stability of the protein, the interaction and the number of contact between the insulin and dicyanamide imidazolium ionic liquids with different alkyl chain length are further analyzed. It is found that the cation stabilize effectively the molecular structure of insulin which relies mainly on the electrostatic interaction between the insulin and the 1-methylimidazole of cation. Comparing to ionic liquids with long alkyl chain, the interaction between the insulin and ionic liquids is more powerful, and the insulin also adsorb more anion and 1-methylimidazole of cation in ionic liquids with short alkyl chain. All these results indicate that the ionic liquids with short chain alkyl indeed improve the molecular structural stability of insulin. Generally, the molecular dynamic simulation, as adopted to this research, provides a molecular insight to investigate the stability of insulin in ionic liquids, which is important and essential for molecular design of ionic liquids and stability study of heat-sensitive protein drugs.

Key words: ionic liquids, insulin, protein stability, interaction energy, molecular simulation

中图分类号:

O6-39

潘晓莉, 李代禧, 魏冬青. 离子液体中胰岛素结构稳定性的分子动力学模拟[J]. 化工学报, 2016, 67(12): 5215-5221.

PAN Xiaoli, LI Daixi, WEI Dongqing. Structural stability of insulin in imidazolium ionic liquids by molecular simulation[J]. CIESC Journal, 2016, 67(12): 5215-5221.

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离子液体中胰岛素结构稳定性的分子动力学模拟

Structural stability of insulin in imidazolium ionic liquids by molecular simulation

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