Simulation of the Functional Dynamics of Bacteriohodopsin in the Integral Purple Membrane

整体紫膜中细菌视紫红质功能动力学的模拟

• 批准号: 9982629
• 负责人: Klaus Schulten
• 金额: $ 37.5万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-15 至 2003-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9982629&HistoricalAwards=false
• 关键词: Simulation; Functional; Dynamics; Bacteriohodopsin; Integral

SchultenMCB 9982629Vectorial proton translocation through membranes is a fundamental energy conversion process in biological cells. Bacteriorhodopsin (bR) is a membrane protein that acts as a light-driven, voltage sensitive proton pump in the purple membrane (PM) of Halobacterium salinarium and achieves its biological function by cycling through a reaction that includes ultrafast (~ 500fs), intermediate (micro), and slow (~10ms) processes in its photo-cycle. The simulation of the photo-process and the first intermediates of bR's photo-cycle in the integral PM will be carried out in order to explain the pump mechanism. Internal water that participates in proton pumping is fundamental for an understanding of the function of bR. Several water molecules have been resolved now crystallographically. Free energy perturbation theory has also been used to successfully place water molecules in bR in modeling studies. Simulations have also revealed that water molecules become displaced during the photo-cycle. The latter calculations depend on the quality of the force fields for water-peptide interactions that still need to be improved. This project will (i) use molecular dynamics (MD) tools and build a realistic model of the PM, including all of its protein, lipid and water components; (ii) apply a new generation of water-peptide potentials to describe bR's internal water; (iii) use the PM model to investigate through MD simulations the influence of hydration on structural properties of the PM; (iv) furnish multiple potential energy surfaces for the retinal chromophore of bR in the ground and excited state, as a function of relevant internal coordinates and including conical intersection to the ground state; (v) carry out quantum dynamical calculations of the primary photoreaction; and (vi) characterize the photocycle intermediates K, L and M using classical molecular dynamics simulations.Bacteriorhodopsin is of utmost simplicity in comparison with other proton translocating bioenergetic proteins and, therefore, constitutes an ideal model for the study of the reaction process. The purple membrane of Halobacterium salinarium involves a highly structured supramolecular organization, and is fundamental for the in vivo functioning of Bacteriorhodopsin.

质子通过细胞膜的矢量易位是生物细胞中一种基本的能量转换过程。Bacteriorhodopsin （bR）是一种膜蛋白，在盐盐杆菌（Halobacterium salinarium）的紫色膜（PM）中起着光驱动、电压敏感的质子泵的作用，并通过在其光循环中进行超快（~ 500fs）、中速（微）和慢速（~10ms）的反应循环来实现其生物学功能。为了解释泵浦的机理，我们将对整体PM中的光过程和bR光循环的第一中间体进行模拟。参与质子泵送的内部水是理解bR功能的基础。几个水分子现在已经在晶体学上被分解了。自由能微扰理论也被用来成功地在模拟研究中放置水分子。模拟还揭示了水分子在光循环过程中发生位移。后者的计算取决于水-肽相互作用的力场的质量，这仍然需要改进。该项目将(i)使用分子动力学（MD）工具并建立PM的现实模型，包括其所有蛋白质，脂质和水成分；（ii）应用新一代的水肽电位来描述bR的内部水；（iii）利用PM模型通过MD模拟研究水化作用对PM结构特性的影响；（iv）为bR在基态和激发态的视网膜发色团提供多个势能面，作为相关内部坐标的函数，包括与基态的圆锥相交；(v)进行初级光反应的量子动力学计算；（vi）利用经典分子动力学模拟表征光循环中间体K、L和M。与其他质子易位的生物能蛋白相比，细菌视紫红质是最简单的，因此，它构成了研究反应过程的理想模型。盐盐杆菌的紫色膜是一个高度结构化的超分子组织，是细菌视紫红质在体内功能的基础。