Surfing on protein folding energy landscapes
Surfing on protein folding energy landscapes
复制标题
在蛋白质折叠能量景观中冲浪
DOI：
10.1073/pnas.012686599
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发表时间：
2002
影响因子：
11.1
通讯作者：
L. Serrano
中科院分区：
文献类型：
--
作者：
J. Schymkowitz;F. Rousseau;L. Serrano
所谓的蛋白质折叠新观点用漏斗形能量景观描述了该过程 (1, 2)。在这种观点中，蛋白质折叠至其天然状态的驱动力源于能量景观向天然构象的强烈倾斜。然而，这可以通过能量景观的粗糙度来抵消，这可能导致折叠反应效率降低，这种现象称为挫败。近年来蛋白质折叠界的一个主要问题是蛋白质拓扑和序列在确定蛋白质折叠机制中的相对重要性。在本期 PNAS (3) 中，Shea 等人。研究蛋白质拓扑和蛋白质序列对能源景观挫败的贡献。谢伊等人。研究蛋白质拓扑和蛋白质序列对能源景观挫败的贡献。
自“莱文塔尔悖论”（4）提出以来，已经过去了 30 多年。 Levinthal计算出，多肽链不可能通过探索整个构象空间来找到其天然状态。因此，必须存在某种搜索算法，从而提出蛋白质通过特定途径折叠到天然构型的建议。为了解决这个悖论，人们提出了不同的折叠机制。由于所有模型的详细描述超出了本评论的范围，因此简要探讨了三个主要思路。在成核生长模型中，(5) 形成一个或多个临界动力核，其余结构围绕其生长。另一个模型系列，例如框架模型，（6）设想形成二级结构元素，然后这些元素对接以在速率限制步骤中形成三级相互作用。最后，在疏水塌陷模型中，(7)考虑了疏水效应……
The so-called new view of protein folding describes the process in terms of funnel-shaped energy landscapes (1, 2). In this view, the drive for a protein to fold to its native state originates from a strong slope of the energy landscape toward native conformations. However, this can be counteracted by roughness of the energy landscape that could render the folding reaction less effective, a phenomenon called frustration . A major question occupying the protein folding community in recent years is the relative importance of protein topology and sequence in determining the folding mechanism of proteins. In this issue of PNAS (3), Shea et al. investigate the contribution of protein topology and protein sequence to the frustration of energy landscapes. Shea et al. investigate the contribution of protein topology and protein sequence to the frustration of energy landscapes.
More than 30 years have passed since the “Levinthal Paradox” (4) was formulated. Levinthal calculated that it is impossible for a polypeptide chain to find its native state by exploring the entire conformational space. Therefore, some kind of search Algorithm has to exist which led to the proposal that proteins fold via specific pathways to the native configuration. Different mechanisms for folding were proposed to solve the paradox. Because a detailed description of all of the models is outside the scope of this commentary, the three main lines of thought are briefly explored. In the nucleation-growth model , (5) one or more critical kinetic nuclei are formed, around which the rest of the structure grows. Another family of models, such as the framework model , (6) envisages the formation of secondary structure elements followed by the docking of those elements to form tertiary interactions in the rate limiting step. Finally, in the hydrophobic collapse model , (7) the hydrophobic effect is considered …
影响因子：
5.6
作者：
Li, AJ;Daggett, V
通讯作者：
Daggett, V
DOI：
10.1016/s1359-0278(96)00060-0
发表时间：
1996-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
Onuchic, JN;Socci, ND;Wolynes, PG
通讯作者：
Wolynes, PG