Atomic-level observation of macromolecular crowding effects: Escape of a protein from the GroEL cage
Atomic-level observation of macromolecular crowding effects: Escape of a protein from the GroEL cage
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DOI：
10.1073/pnas.0535055100
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发表时间：
2003-03-04
影响因子：
11.1
通讯作者：
Elcock, AH
中科院分区：
文献类型：
--
作者：
Elcock, AH
实验工作已经证明，GroEL-GroES伴侣蛋白机器的有效操作对大分子拥挤剂的存在敏感。在这里，我描述了原子详细的计算机模拟，提供了一个微观的观点，如何拥挤的影响。进行模拟以计算从GroEL的中心腔提取蛋白质罗丹酸盐到含有一系列拥挤浓度的溶液中所需的自由能。计算的能量允许折叠蛋白质的总产率进行预测;计算的产量显示出与实验观察到的相同的拥挤剂的浓度的非线性依赖。模拟和实验之间的密切对应，提示使用前者在一个真正的预测设置：模拟被用来表明，更有效的拥挤剂可能会被设计利用“广场恐惧症的影响”。
Experimental work has demonstrated that the efficient operation of the GroEL-GroES chaperonin machinery is sensitive to the presence of macromolecular crowding agents. Here, I describe atomically detailed computer simulations that provide a microscopic view of how crowding effects are exerted. Simulations were performed to compute the free energy required to extract the protein rhodanese from the central cavity of GroEL into solutions containing a range of crowder concentrations. The computed energetics allow the total yield of folded protein to be predicted; the calculated yields show a nonlinear dependence on the concentration of crowding agent identical to that observed experimentally. The close correspondence between simulation and experiment prompts the use of the former in a truly predictive setting: simulations are used to suggest that more effective crowding agents might be designed by exploiting an "agoraphobic effect".