分子动力学模拟研究点突变(Met108→Leu108)对树胶醛糖结合蛋白与配体作用的影响

doi:10.7503/cjcu20130889

高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (2): 338.doi: 10.7503/cjcu20130889

分子动力学模拟研究点突变(Met108→Leu108)对树胶醛糖结合蛋白与配体作用的影响

冯献礼¹, 李卓¹, 赵熹¹, 于辉², 刘慧玲¹, 黄旭日¹()

1. 吉林大学理论化学研究所, 理论化学计算国家重点实验室, 长春 130021
2. 北华大学化学与生物学院, 吉林 132013

收稿日期:2013-09-11 出版日期:2014-02-10 发布日期:2014-01-02
作者简介:联系人简介: 黄旭日, 男, 博士, 教授, 博士生导师, 主要从事化学微观过程及反应控制理论研究. E-mail:huangxr@jlu.edu.cn
基金资助:
国家“九七三”计划项目(批准号: 2012CB932800)和国家自然科学基金(批准号: 21173097, 21103066)资助

Molecular Dynamics Simulation Study on the Effect of Mutant(Met108→Leu108) on Interactions Between Arabinose-binding Protein and Ligand^†

FENG Xianli¹, LI Zhuo¹, ZHAO Xi¹, YU Hui², LIU Huiling¹, HUANG Xuri^1,^*()

1. State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130021, China
2. School of Chemistry and Biology, Beihua University, Jilin 132013, China

Received:2013-09-11 Online:2014-02-10 Published:2014-01-02
Contact: HUANG Xuri E-mail:huangxr@jlu.edu.cn
Supported by:
† Supported by the for National Basic Research Program of China(No.2012CB932800) and the National Natural Science Foundation of China(Nos.21173097211, 21103066)

摘要/Abstract

摘要：

为了研究点突变(Met108→Leu108)对树胶醛糖结合蛋白(ABP)与配体结合能力的影响, 对ABP、 ABP结合树胶醛糖复合物及ABP结合半乳糖复合物以及它们各自的突变体分别进行60 ns的分子动力学模拟. 模拟结果表明, 108号残基突变前后, 电子等排体的两个氨基酸残基, 使蛋白与配体间的范德华相互作用发生明显变化, 同时导致蛋白的内部运动也发生变化, 进而影响蛋白与配体的相互作用. 进一步分析表明, 突变前后的蛋白构象变化都趋向于两个结构域张开, 而与配体的结合可减缓张开程度.

关键词: 树胶醛糖结合蛋白, 分子动力学, 非极性相互作用

Abstract:

In order to understand the effect of the mutant(Met108→Leu108) of the arabinose-binding protein(ABP) on the interactions between the protein and ligand, a series of 60 ns molecular dynamics simulations for the ABP, ABP bound ARA, ABP bound GAL and their mutants was performed, respectively. The results show that the mutation(Met108→Leu108) in ABP leads to the significant change of the van der Waals interaction between residue 108 and ligand, which further causes the changes of the protein’s internal motion and interactions between the protein and ligand. The varieties in interaction between the protein and ligand make the two globular domains of wild-type and mutation-type of ABP gradually open and the ligand binding can control the open movement of the protein.

Key words: Arabinose-binding protein, Molecular dynamics simulation, Non-polar interaction

中图分类号:

O641.12⁺1

TrendMD:

冯献礼, 李卓, 赵熹, 于辉, 刘慧玲, 黄旭日. 分子动力学模拟研究点突变(Met108→Leu108)对树胶醛糖结合蛋白与配体作用的影响. 高等学校化学学报, 2014, 35(2): 338.

FENG Xianli, LI Zhuo, ZHAO Xi, YU Hui, LIU Huiling, HUANG Xuri. Molecular Dynamics Simulation Study on the Effect of Mutant(Met108→Leu108) on Interactions Between Arabinose-binding Protein and Ligand^†. Chem. J. Chinese Universities, 2014, 35(2): 338.

图/表 9

Fig.1 Overview of protein ABP and ligand ARA(ball-and-stick) ABP color is marked by secondary structure.

Fig.2 Time evolution of backbone RMSD of the ABP bound ARA(a), ABP(b), ABP bound GAL(c)(A) and their corresponding mutants(a, b and c, B)

Fig.3 Radius of gyration of the ABP bound ARA(a), ABP(b), ABP bound GAL(c)(A) and their corresponding mutants(a, b and c, B)

Fig.4 Overlapping of the ABP molecular dynamics simulation structures at 0.2(green) and 50 ns(red)

Fig.5 Root mean square fluctuation(RMSF) of the Cα atoms around the average MD structures (A) a. ABP bound ARA; b. ABP bound GAL; (B) a. mutant ABP bound ARA; b. mutant ABP bound GAL.

Fig.6 Hydrogen bonding interaction between protein and ligand(A) ABP bound GAL; (B) ABP bound ARA; (C) mutant ABP bound GAL; (D) mutant ABP bound ARA.

Table 1 Binding free energy components of ABP bound GAL, ABP bound ARA, mutant ABP bound GAL and mutant ABP bound ARA complexes

System	E_coul/(kJ·mol^-1)	E_vdw/(kJ·mol^-1)	E_Total/(kJ·mol^-1)
ABP bound GAL	-122.813	-5.11859	-127.93
ABP bound ARA	-164.561	-62.7825	-227.34
Mutant ABP bound GAL	-173.963	-78.6312	-252.59
Mutant ABP bound ARA	-106.336	-4.034	-110.37

Fig.7 Distance of the pairs of atoms which are specified(A) a. ABP bound ARA, Met108 CE—(GAL C5); b. ABP bound ARA, Met108 CE—(GAL C5); (B) a. mutant ABP bound GAL, Leu108 CD1—(Pro254 CB); b. mutant ABP bOUND ARA, Leu108 CD1—(Pro254 CB).

Fig.8 Principal collective motions of the systems of ABP bound ARA(A), ABP bound GAL(B), mutant ABP bound ARA(C) and mutant ABP bound GAL(D) described by the first eigenvector represented as the red structure transforms into the blue structures as it moving in the direction

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分子动力学模拟研究点突变(Met108→Leu108)对树胶醛糖结合蛋白与配体作用的影响

Molecular Dynamics Simulation Study on the Effect of Mutant(Met108→Leu108) on Interactions Between Arabinose-binding Protein and Ligand^†

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