| 引用本文: | 张桥石,李灌澍,窦薛楷,薛友林,宋有涛.DnaK蛋白扭链残基突变体影响其ATPase活性的分子动力学模拟研究[J].生物信息学,2016,14(3):139-145. |
| ZHANG Qiaoshi,LI Guanshu,DOU Xuekai,XUE Youlin,SONG Youtao.Using molecular dynamics simulation to study the effects of the ATPase activity in mutants of hinge residues of Dnak[J].Chinese Journal of Bioinformatics,2016,14(3):139-145. |
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| 摘要: |
| 大肠杆菌分子伴侣蛋白DnaK氮端核苷酸结合域(NBD, nucleotide-binding domain)的II-A和II-B子域之间的一些高度保守的扭链残基突变后(I202A, S203A, G223A, L227A, G228A),其ATPase活性也发生变化原因不清楚。我们通过同源建模的方法构建NBD与小分子ATP相互作用的各蛋白模型,使用分子动力学模拟方法研各模型的结构变化并尝试找出其与ATPase活性变化的关系。结果表明,除L227A外,所有突变模型T11烃基与ATP-γ磷酸基团间的距离与活性变化间具有明显规律；但是所有模型中,能影响与DnaJ结合,从而影响ATPase活性的β220(214-221)部分的紧致性变化符合规律,进一步的蛋白对接实验证实了这一点,所以这些扭链残基突变体可能主要是通过这两个部分的变化,引起ATPase活性的改变。 |
| 关键词: DnaK 扭链残基 同源建模 分子动力学模拟 蛋白对接 |
| DOI：10.3969/j.issn.1672-5565.2016.03.03 |
| 分类号:Q523 |
| 文献标识码:A |
| 基金项目:国家自然科学基金项目(31570154)；国家自然科学基金项目(31201285)。 |
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| Using molecular dynamics simulation to study the effects of the ATPase activity in mutants of hinge residues of Dnak |
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ZHANG Qiaoshi1, LI Guanshu2, DOU Xuekai2, XUE Youlin3, SONG Youtao1,2
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(1. College of Life Science, Liaoning University, Shenyang 110036, China; 2. School of Environmental Science, Liaoning University, Shenyang 110036, China; 3. College of Light Industry, Liaoning University, Shenyang 110036, China)
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| Abstract: |
| When the highly conserved hinge residues (I202, S203, G223, L227, G228), which are located in the subdomain II-A and II-B of NBD (Nucleotide binding domain) in the E.coil’sDnak, mutate into alanine. It is not clear that the change reason of ATPase activity. We build all of the wild type and mutant protein model which contain small molecule ATP by using the method of homologous modeling, than using the molecular dynamics simulation (MDs) to study the comformational change of these mutants, and want to find the relationship with the change of ATPase activity. Results show that the distances between the hydroxyl of Tyr11 residue and the γ phosphate of ATP in all models expect L227A have obvious rules with the activity of ATPase; but the change of compactness in β220 (214-221), which can impact the binding of DnaJ and effect the activity of ATPase, conform to the rules. The further experiment of protein docking confirm it, so the mutants of hinge residues may influence the ATPase activity by the changes of these two parts. |
| Key words: DnaK Hinge residues Homologous modeling Molecular dynamics simulation Protein docking |
