Bui Phuong Thuy, Hoang Trinh Xuan
Center for Computational Physics, Institute of Physics, Vietnam Academy of Science and Technology, 10 Dao Tan, Ba Dinh, Hanoi, Vietnam.
J Chem Phys. 2016 Mar 7;144(9):095102. doi: 10.1063/1.4943042.
We investigate the interplay between post-translational folding and escape of two small single-domain proteins at the ribosomal exit tunnel by using Langevin dynamics with coarse-grained models. It is shown that at temperatures lower or near the temperature of the fastest folding, folding proceeds concomitantly with the escape process, resulting in vectorial folding and enhancement of foldability of nascent proteins. The concomitance between the two processes, however, deteriorates as temperature increases. Our folding simulations as well as free energy calculation by using umbrella sampling show that, at low temperatures, folding at the tunnel follows one or two specific pathways without kinetic traps. It is shown that the escape time can be mapped to a one-dimensional diffusion model with two different regimes for temperatures above and below the folding transition temperature. Attractive interactions between amino acids and attractive sites on the tunnel wall lead to a free energy barrier along the escape route of the protein. It is suggested that this barrier slows down the escape process and consequently promotes correct folding of the released nascent protein.
我们使用粗粒度模型的朗之万动力学，研究了两种小的单结构域蛋白在核糖体出口通道处的翻译后折叠与逃逸之间的相互作用。结果表明，在低于或接近最快折叠温度时，折叠与逃逸过程同时进行，导致新生蛋白的矢量折叠和折叠能力增强。然而，随着温度升高，这两个过程之间的同步性会变差。我们的折叠模拟以及使用伞形采样进行的自由能计算表明，在低温下，通道内的折叠遵循一到两条特定路径，没有动力学陷阱。结果表明，对于高于和低于折叠转变温度的温度，逃逸时间可以映射到具有两种不同状态的一维扩散模型。氨基酸与通道壁上的吸引位点之间的吸引相互作用导致沿着蛋白质逃逸路径的自由能障碍。有人认为，这种障碍减缓了逃逸过程，从而促进了释放的新生蛋白的正确折叠。
