Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary.
Sci Rep. 2021 May 12;11(1):10059. doi: 10.1038/s41598-021-89169-5.
RalF is an Arf GEF from Legionella pneumophilia, the bacterium that causes severe pneumonia. In its crystal structure, RalF is in the autoinhibited form. A large-scale domain motion is expected to lift the autoinhibition, the mechanism of which is still unknown. Since RalF is activated in the presence of the membrane, its active structure and the structure of the RalF-Arf1 complex could not have been determined experimentally. On the simulation side, it has been proven that classical Molecular Dynamics (MD) alone is not efficient enough to map motions of such amplitude and determine the active conformation of RalF. In this article, using Molecular Dynamics with excited Normal Modes (MDeNM) combined with previous experimental findings we were able to determine the active RalF structure and the structure of the RalF-Arf1 complex in the presence of the membrane, bridging the gap between experiments and simulation.
RalF 是来自嗜肺军团菌的 Arf GEF，该细菌会引起严重肺炎。在其晶体结构中，RalF 处于自动抑制状态。预计会发生大规模的结构域运动以解除自动抑制，但具体机制尚不清楚。由于 RalF 在膜的存在下被激活，因此其活性结构和 RalF-Arf1 复合物的结构无法通过实验确定。在模拟方面，已经证明仅使用经典分子动力学 (MD) 不足以映射如此幅度的运动并确定 RalF 的活性构象。在本文中，我们使用结合了兴奋正则模态的分子动力学 (MDeNM) 并结合先前的实验结果，成功确定了膜存在下的活性 RalF 结构和 RalF-Arf1 复合物的结构，在实验和模拟之间架起了桥梁。
