分子动力学研究F_1-ATP合酶对三磷酸腺苷的稳定和定位作用（英文）

F_1-ATPase Stabilizes and Positions Adenosine Triphosphate Revealed by Molecular Dynamics Simulations

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.

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.