基于分子对接研究小分子对冰核蛋白的微观抑制机理

胡响响; 丁雅丽; 冯玄; 张然; 石彤非; 卫来

doi:10.14135/j.cnki.1006-3080.20201218002

基于分子对接研究小分子对冰核蛋白的微观抑制机理

doi: 10.14135/j.cnki.1006-3080.20201218002

胡响响^1,,
丁雅丽¹,
冯玄^{2, 3},
张然^2, ,,
石彤非^{2, 3, ,},
卫来¹

1.
伊犁师范大学物理科学与技术学院，新疆凝聚态相变与微结构实验室，新疆伊宁 835000
2.
中科院长春应用化学研究所，高分子物理与化学国家重点实验室，长春 130022
3.
中国科学技术大学，应用化学与工程学院，合肥 230026

基金项目: 国家自然科学基金(21674114)

详细信息

作者简介:
胡响响（1996—），男，河南睢县人，硕士生，主要研究方向为高分子物理。E-mail：xxhu@ciac.ac.cn

通讯作者:
张　然，E-mail：rzhangciac@ciac.ac.cn

石彤非，E-mail：tfshi@ciac.ac.cn

中图分类号: O641
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- 被引次数: 0
出版历程
- 收稿日期: 2020-12-18
- 网络出版日期: 2021-02-07

Microscopic Inhibition Mechanism of Small Molecules on Ice Nucleation Protein Based on Molecular Docking

HU Xiangxiang^1
,,
DING Yali¹,
FENG Xuan^{2, 3},
ZHANG Ran^{2
, ,},
SHI Tongfei^{2, 3
, ,},
WEI Lai¹

1.
Xinjiang Laboratory of Phase Transitions and Microstructures in Condensed Matter Physics, College of Physical Science and Technology, Yili Normal University, Yining 835000, Xinjiang, China
2.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
3.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China

摘要

摘要: 自然界广泛存在着的冰核蛋白(INP)能够在微观尺度诱导水分子规整排列，提高冰点，而其蛋白三级结构仍未能通过实验确定。最新研究表明冰核蛋白具有与抗冻蛋白(AFP)结构相同的冰结合模板TXT，但INP模板面积更大导致其功能与AFP完全相反。相关研究表明INP可通过酪氨酸(TYR)阶梯结构二聚化形成新的β-螺旋二聚体进而增加结冰活性表面积来促进冰核的形成。同时在一系列对照实验中，发现聚甘油能够结合并抑制冰核细菌丁香假单胞菌INP的冰成核活性。因此，本文通过使用分子模拟软件AutoDock研究甘油和三聚甘油分子与北方假单胞菌的冰核蛋白模型之间的相互作用，以期阐释该抑制行为的分子机理以及是否在冰核蛋白类结构中具有普适性。结合信息显示了配体分子与TXT结冰模板和TYR阶梯结构之间的不同结合能力，并且在与TXT结冰模板的结合中发现有冰核蛋白其他残基参与结合。模拟结果表明配体分子与INP的特异性结合可能适用于其他具有类似结构的INP。该结果为聚甘油作为冷冻保护材料的开发和进一步理解冰核蛋白结冰机理提供了有用的理论信息。
- 冰核蛋白 /
- 分子建模 /
- AutoDock /
- 聚甘油 /
- 北方假单胞菌
Abstract: Ice nucleation proteins (INPs), which exist widely in nature, can induce water molecules to arrange regularly at micro scale resulting in elevated freezing point, but their tertiary structures have not been determined by experiments. The latest research shows that INPs may interact with water molecules to promote the formation of ice nuclei through TXT template of central repeat region, which shares identical structural feature of antifreeze proteins but with larger template area and opposite functionalities. INPs also have tyrosine (TYR) ladders to form new β−helix dimer along dimerization interface, thus increasing the active surface area of protein ice. At the same time, in a series of control experiments, it was found that polyglycerol at a certain concentration obviously combined with the INP of ice nucleation bacteria Pseudomonas syringae and inhibited its ice nucleation activity. In this work, molecular simulation software AutoDock was used to study the binding interaction of ice nucleation protein model of Pseudomonas borealis with glycerol and triglycerol molecules, in order to discover the corresponding inhibition mechanism on ice nucleation proteins and its universality with other INPs. The binding information shows that the ligand molecules express different binding abilities to TXT template and tyrosine ladder, and other residues of ice nucleation protein may participate in the binding with TXT freezing template.
- Ice nucleation protein /
- Molecular modeling /
- AutoDock /
- Polyglycerol /
- Pseudomonas Borealis

HTML全文

图 1 PbINP的三维模型

Figure 1. Three-dimension model of PbINP

a-Cartoon model of PbINP; b-Tyrosine ladder side view; c-TXT freezing surface

下载: 全尺寸图片幻灯片

图 2 冰核蛋白模拟过程中产生的结构相对于初始结构的均方根偏差(RMSD)，以及模拟结束时INP单体和二元体的空间结构视图(其中图(c)和(e)是图(b)和(d)中结构的俯视图)

Figure 2. Root mean square deviation (RMSD) of the structure produced during the simulation of ice nucleation protein with respect to the initial structure, and the views of the spatial structure of INP monomer and binary body at the end of simulation (in which Fig. (c) and (e) are the top views of the structures in Fig. (b) and (d)).

下载: 全尺寸图片幻灯片

图 3 配体分子与PbINP的结合模式

Figure 3. Binding modes of ligand molecule and PbINP

下载: 全尺寸图片幻灯片

表 1 配体分子与酪氨酸残基对接结果

Table 1. Result of ligand molecule docking TYR residues

Ligand	Residue site	Binding energy/ (kcal·mol⁻¹)	k_i/ (μmol·L⁻¹)	Number of same clusters
Glycerol	18, 34, 50	−3.8	1630	157
	18, 34, 50	−4.87	267.15	23
	50, 66, 82	−3.5	2720	97
	50, 66, 82	−4.76	323.22	40
	98, 114, 130	−4.13	946.85	83
	98, 114, 130	−4.81	295.71	52
Triglycerol	18, 34,5 0, 66, 82	−3.72	1870	234
Triglycerol	66, 82, 98, 114, 130	−4.63	404.52	162

下载: 导出CSV

表 2 配体分子与苏氨酸残基对接结果

Table 2. Result of ligand molecule docking THR residues

Ligand	Residue site	Binding energy/ (kcal·mol⁻¹)	k_i/ (μmol·L⁻¹)	Number of same clusters
Glycerol	5,7,21,23,37, 39	−5.47	98.41	122
	5,7,21,23,37, 39	−6.89	8.93	72
	53,55,69,71, 85 ,87	−6.18	29.32	152
	101,103,117, 119,133,135	−6.41	19.92	186
Triglycerol	5,21,37,53	−5.57	82.22	155
	7,23,39,55	−3.82	1580	187
	7,23,39,55	−5.37	115.98	108
	37,53,69,85	−5.25	142.24	233
	39,55,71,87	−4.8	303.56	292
	85,101,117,133	−5.0	217.51	139
	87,103,119,135	−6.83	9.78	249

下载: 导出CSV

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