小分子促进抗冻蛋白抗冻效果的分子机制

doi:10.19894/j.issn.1000-0518.210018

摘要/Abstract

摘要： 抗冻蛋白(Antifreeze proteins,AFPs)是一种来自少数鱼类、昆虫、细菌等生物的大分子抗冻剂,能够通过降低溶液的冰点而不影响熔点的方式保护生物体免于冰冻伤害。 AFP在食物冷藏、组织和器官保存以及提高经济作物抗冻能力等领域都有巨大的潜在应用价值。目前,还有许多有关AFP作用机制的问题尚未解决。为揭示如甘油、海藻糖和柠檬酸等小分子促进抗冻蛋白抗冻效果的分子机理,使用AutoDock对接软件模拟研究抗冻蛋白DAFP-1与小分子之间的潜在多种结合方式。通过对结合自由能、对接构象等性质的对比和分析,发现小分子促进抗冻行为的物理机制不仅仅局限于实验推测的Arg9残基与小分子之间的单一结合作用,而且能够通过如Arg30、Arg54等组合位点对接的方式促成DAFP-1蛋白之间的多聚体,从而提高DAFP-1的抗冻能力。

关键词: 抗冻蛋白, 精氨酸, 小分子, 分子对接

Abstract: Antifreeze proteins (AFPs) are able to generate a difference between the non-equilibrium freezing point and the melting point, which is called thermal hysteresis (TH). AFPs inspire the design of new materials for use in the field of food industry and biomedical applications such as cell and organ preservation. The TH activity of a specific AFP of a beetle named Dendroides canadensis (DAFP-1) can be enhanced by low molecular mass molecules such as glycerol, trehalose and citrate acid, however the mechanism remains elusive. In order to reveal the molecular mechanism of the corresponding enhancing effects, we use AutoDock4.2 software to explore the potential docking modes between DAFP-1 and these low molecular mass molecules. Through the comparison and analysis of binding energy and docking conformations, it is found that the physical mechanism of low molecular mass molecules promoting antifreeze activity is not only limited to the single site binding between Arg9 residues and low molecular mass molecules as predicted in literature, the enhancement can also happen through the combined docking sites such as Arg30 and Arg54. These new binding scenarios can promote the aggregation of multiple DAFP-1 proteins forming larger binding templates, which greatly improves the antifreeze activity of DAFP-1.

Key words: Antifreeze proteins, Arginine, Low molecular mass molecules, AutoDock

中图分类号:

O641

丁雅丽, 胡响响, 冯玄, 张然, 石彤非, 卫来. 小分子促进抗冻蛋白抗冻效果的分子机制[J]. 应用化学, 2021, 38(12): 1612-1620.

DING Ya-Li, HU Xiang-Xiang, FENG Xuan, ZHANG Ran, SHI Tong-Fei, WEI Lai. Mechanism of Enhancing Antifreeze Protein Activity by Low Molecular Mass Molecules[J]. Chinese Journal of Applied Chemistry, 2021, 38(12): 1612-1620.

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