物理化学学报 >> 2015, Vol. 31 >> Issue (9): 1803-1809.doi: 10.3866/PKU.WHXB201508062

生物物理化学 上一篇    下一篇

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   

  1. 1 四川师范大学化学与材料科学学院,成都610068
    2 中国科学院理论物理研究所理论物理国家重点实验室,北京100190
  • 收稿日期:2015-04-17 发布日期:2015-09-06
  • 基金资助:
    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)

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

Shao-Gui. WU1,2(),Xiao-Tong. GAO1,Quan. LI1,Jie. LIAO1,Cheng-Gang. XU1   

  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:2015-04-17 Published:2015-09-06
  • Supported by:
    the National Natural Science Foundation of China(11405113);Science and Technology Plan of Sichuan Province,China(2010JY0122);Science Research Fund of Sichuan Normal University, China(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

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: F1-ATPase, Hydrogen bond, Molecular dynamics, Mutation

MSC2000: 

  • O641