Flexibility of the bacterial chaperone trigger factor in microsecond-timescale molecular dynamics simulations.
Flexibility of the bacterial chaperone trigger factor in microsecond-timescale molecular dynamics simulations.
复制标题
微秒时间尺度分子动力学模拟中细菌伴侣触发因素的灵活性。
DOI：
10.1016/j.bpj.2013.06.028
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发表时间：
2013
影响因子：
3.4
通讯作者：
Elcock,AdrianH
中科院分区：
文献类型：
--
作者：
Thomas,AndrewS;Mao,Suifang;Elcock,AdrianH
细菌伴侣触发因子（TF）是新生蛋白链从核糖体出口通道中出现时遇到的第一个伴侣。实验结果表明，TF具有相当大的构象灵活性，为了从原子水平上观察这种灵活性，我们使用两个不同的模拟力场（OPLS-AA/L和AMBER ff99SB-ILDN）对TF在显式溶剂中的1.5 μs分子动力学进行了独立的模拟。两种模拟都表明，TF具有巨大的灵活性，由于蛋白质组成结构域的重新定向而引起的巨大的晶体结构偏移；这两种模拟也预测了TF的PPIase结构域和参与新生链结合的Arm 1结构域之间形成广泛的接触。然而，在OPLS模拟中，TF迅速稳定成一个非常紧凑的构象，持续至少1μs，而在AMBER模拟中，它保持高度动态；在另外的模拟中，两个力场交换表明，这些差异至少部分归因于采样问题。模拟结果为一些关于TF构象行为的实验观察提供了潜在的合理化，并对使用模拟来模拟TF在翻译核糖体上的功能具有启示意义。
The bacterial chaperone trigger factor (TF) is the first chaperone to be encountered by a nascent protein chain as it emerges from the ribosome exit tunnel. Experimental results suggest that TF possesses considerable conformational flexibility, and in an attempt to provide an atomic-level view of this flexibility, we have performed independent 1.5-μs molecular dynamics simulations of TF in explicit solvent using two different simulation force fields (OPLS-AA/L and AMBER ff99SB-ILDN). Both simulations indicate that TF possesses tremendous flexibility, with huge excursions from the crystallographic conformation caused by reorientations of the protein's constituent domains; both simulations also predict the formation of extensive contacts between TF's PPIase domain and the Arm 1 domain that is involved in nascent-chain binding. In the OPLS simulation, however, TF rapidly settles into a very compact conformation that persists for at least 1μs, whereas in the AMBER simulation, it remains highly dynamic; additional simulations in which the two force fields were swapped suggest that these differences are at least partly attributable to sampling issues. The simulation results provide potential rationalizations of a number of experimental observations regarding TF's conformational behavior and have implications for using simulations to model TF's function on translating ribosomes.