Lindorff-Larsen Kresten, Maragakis Paul, Piana Stefano, Shaw David E
D. E. Shaw Research , New York, New York 10036, United States.
Department of Biochemistry and Molecular Biophysics, Columbia University , New York, New York 10032, United States.
J Phys Chem B. 2016 Aug 25;120(33):8313-20. doi: 10.1021/acs.jpcb.6b02024. Epub 2016 May 9.
Human ubiquitin has been extensively characterized using a variety of experimental and computational methods and has become an important model for studying protein dynamics. Nevertheless, it has proven difficult to characterize the microsecond time scale dynamics of this protein with atomistic resolution. Here we use an unbiased computer simulation to describe the structural dynamics of ubiquitin on the picosecond to millisecond time scale. In the simulation, ubiquitin interconverts between a small number of distinct states on the microsecond to millisecond time scale. We find that the conformations visited by free ubiquitin in solution are very similar to those found various crystal structures of ubiquitin in complex with other proteins, a finding in line with previous experimental studies. We also observe weak but statistically significant correlated motions throughout the protein, including long-range concerted movement across the entire β sheet, consistent with recent experimental observations. We expect that the detailed atomistic description of ubiquitin dynamics provided by this unbiased simulation may be useful in interpreting current and future experiments on this protein.
人类泛素已通过多种实验和计算方法得到广泛表征，并已成为研究蛋白质动力学的重要模型。然而，事实证明，以原子分辨率表征该蛋白质在微秒时间尺度上的动力学是困难的。在此，我们使用无偏计算机模拟来描述泛素在皮秒到毫秒时间尺度上的结构动力学。在模拟中，泛素在微秒到毫秒时间尺度上在少数几种不同状态之间相互转换。我们发现，溶液中游离泛素所呈现的构象与泛素与其他蛋白质形成复合物的各种晶体结构中所发现的构象非常相似，这一发现与先前的实验研究一致。我们还观察到整个蛋白质中存在微弱但具有统计学意义的相关运动，包括跨越整个β折叠的长程协同运动，这与最近的实验观察结果一致。我们预计，这种无偏模拟所提供的泛素动力学的详细原子描述可能有助于解释关于该蛋白质的当前和未来实验。
