Improved Go-like models demonstrate the robustness of protein folding mechanisms towards non-native interactions
Improved Go-like models demonstrate the robustness of protein folding mechanisms towards non-native interactions
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DOI：
10.1016/j.jmb.2003.09.047
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发表时间：
2003-11-21
影响因子：
5.6
通讯作者：
Brooks, CL
中科院分区：
文献类型：
--
作者：
Karanicolas, J;Brooks, CL
使用简单的理论模型为我们目前对蛋白质从大量可用的未折叠状态中采用其天然折叠方式的理解提供了相当大的贡献。在构建可计算的可处理模型时，一个常见的假设是忽略了在描述为“G (o) over baro-like”的模型类中稳定非原生相互作用。本研究的重点是通过G (o) over bar -like模型来表征许多蛋白质的折叠，该模型旨在将反映蛋白质序列的最大信息量映射到“极简”骨架上。该模型包含足够的信息来重现许多蛋白质的折叠过渡状态，包括通过不同过渡状态折叠的拓扑类似蛋白质。值得注意的是，这些模型也证明了与被认为是由非原生相互作用稳定的折叠过渡态的一般特征的一致性。这表明原生相互作用是大多数蛋白质折叠过渡态的主要决定因素，而非原生相互作用仅导致局部结构扰动。本文还预测了噬菌体λ蛋白W的不对称折叠过渡态，但尚未进行实验表征。(C) 2003 Elsevier Ltd.版权所有。
The use of simple theoretical models has provided a considerable contribution to our present understanding of the means by which proteins adopt their native fold from the plethora of available unfolded states. A common assumption in building computationally tractable models has been the neglect of stabilizing non-native interactions in the class of models described as "G (o) over baro-like." The focus of this study is the characterization of the folding of a number of proteins via a G (o) over bar -like model, which aims to map a maximal amount of information reflecting the protein sequence onto a "minimalist" skeleton. This model is shown to contain sufficient information to reproduce the folding transition states of a number of proteins, including topologically analogous proteins that fold via different transition states. Remarkably, these models also demonstrate consistency with the general features of folding transition states thought to be stabilized by non-native interactions. This suggests that native interactions are the primary determinant of most protein folding transition states, and that non-native interactions lead only to local structural perturbations. A prediction is also included for an asymmetrical folding transition state of bacteriophage lambda protein W, which has yet to be subjected to experimental characterization. (C) 2003 Elsevier Ltd. All rights reserved.