分子动力学研究F<sub>1</sub>-ATP合酶对三磷酸腺苷的稳定和定位作用

引用本文: 伍绍贵, 高晓彤, 李权, 廖杰, 徐成刚. 分子动力学研究F₁-ATP合酶对三磷酸腺苷的稳定和定位作用[J]. 物理化学学报, 2015, 31(9): 1803-1809. doi: 10.3866/PKU.WHXB201508062 shu

Citation: WU Shao-Gui, GAO Xiao-Tong, LI Quan, LIAO Jie, XU Cheng-Gang. F₁-ATPase Stabilizes and Positions Adenosine Triphosphate Revealed by Molecular Dynamics Simulations[J]. Acta Physico-Chimica Sinica, 2015, 31(9): 1803-1809. doi: 10.3866/PKU.WHXB201508062 shu

分子动力学研究F₁-ATP合酶对三磷酸腺苷的稳定和定位作用

伍绍贵 ^1,2, ,
高晓彤 ^1, ,
李权 ^1, ,
廖杰 ^1, ,
徐成刚 ^1,

基金项目:
国家自然科学基金(11405113) (11405113)

四川省科技厅项目(2010JY0122) (2010JY0122)

四川师范大学科学研究基金(10MSL02)资助 (10MSL02)

摘要:

F₁-ATP合酶通过与ATP之间建立广泛的相互作用, 实现对ATP的位置进行精确的定位. 这些相互作用为ATP的合成/水解创造了稳定的环境. 理解这些相互作用是理解ATP的合成/水解机理的基础. 我们通过分子动力学模拟方法研究这些相互作用, 找出在稳定化过程中起到重要作用的残基. 通过检测ATP和F₁-ATP合酶之间的非键相互作用, 发现残基段158-164所形成的loop区域及残基R189, Y345对ATP存在显著相互作用. 其中, 该loop区域对ATP的三磷酸部分形成一个半包围结构, 封闭活性位点区域, 并通过氢键网络约束ATP三磷酸的运动, 为ATP合成/水解创造稳定的环境. 此外, 关键残基Y345通过π-π叠加相互作用对ATP的碱基进行约束, 但是ATP的碱基可以在平行于Y345芳香环的平面内进行滑动, 我们推断这种滑动运动有利于促进ATP的水解.

关键词:

F₁-ATP合酶
/ 氢键
/ 分子动力学
/ 突变

English

F₁-ATPase Stabilizes and Positions Adenosine Triphosphate Revealed by Molecular Dynamics Simulations

1.
1 College of Chemistry and Material Science, Sichuan Normal University, Chengdu 610068, P. R. China;
2 State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, P. R. China
Received Date: 17 April 2015
Available Online: 06 September 2015
Fund Project:
国家自然科学基金(11405113)

四川省科技厅项目(2010JY0122)

四川师范大学科学研究基金(10MSL02)资助

Abstract:

F₁-ATPase makes extensive interactions with ATP through forming a network of interactions around ATP. These interactions create a steady environment for ATP synthesis/hydrolysis. Thus understanding these interactions between ATP and F₁-ATPase is essential for understanding ATP synthesis/hydrolysis mechanism. We performed all-atom molecular dynamics (MD) simulations to elucidate these interactions and attempted to identify key residues which play important roles in stabilizing and positioning ATP. By examining the non-bonded energies between ATP and residues of βTP subunit in F₁-ATPase, it is found that residues 158-164, R189, Y345 have significant interactions with ATP. The loop segment (residues 158-164) and R189 surround ATP by a half and they interact with β and γ phosphates through forming a network of hydrogen bonds to constraint the motion of ATP triphosphate. The interaction network seals off the conformation of the catalytic site, creating a steady environment for ATP synthesis/hydrolysis. Additionally, ATP base is positioned by the π-π stacking interaction from Y345. However, ATP base can slide and move paralleling to the aromatic group of Y345. It is deduced that this motion may facilitate ATP hydrolysis.

Key words:

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沈阳化工大学材料科学与工程学院沈阳 110142

分子动力学研究F₁-ATP合酶对三磷酸腺苷的稳定和定位作用

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