Design of proteins with selected thermal properties
Design of proteins with selected thermal properties
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DOI：
10.1016/s1359-0278(96)00054-5
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Shakhnovich, EI
中科院分区：
文献类型：
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作者：
Morrissey, MP;Shakhnovich, EI
背景资料：到目前为止，模型蛋白质设计的方法在很大程度上是特设的，产生的序列只能在一些看似任意的模拟温度下折叠。但真实的蛋白质是存在的，而且必须在一个强加的热环境中折叠。需要存在一个序列设计方法的基础上的热力学力学的第一原则，从而包含一个严格的治疗折叠温度。在这项工作中，我们报道了一种合理序列设计的方法，该方法采用目标结构和所需的最佳折叠温度T-Z，并产生预测在折叠温度T-Z下相对于目标结构是生物学稳定的序列。F近似于T-Z。这种“累积量设计方法”是基于平均场高温扩展的分子配分函数。折叠模拟的设计序列证实，在T-Z设计的序列确实折叠最佳时，T-F接近T-Z。结论：累积量的方法是非常成功的设计模型蛋白质，它也提供了一些洞察真实的蛋白质的热性质，照亮的功能，区分耐热和嗜冷（冷）的序列从他们的嗜温对应物。(C)Current Biology Ltd
Background: Methods of model protein design have until now been largely ad hoc, yielding sequences that are foldable only at some seemingly arbitrary simulation temperature. But real proteins exist and must fold within an imposed thermal environment. The need exists for a sequence design method based on statistical-mechanical first principles, thus containing a rigorous treatment of folding temperature.Results: In this work, we report a method of rational sequence design that takes a target structure and a desired optimal folding temperature T-Z and generates a sequence that is predicted to be thermodynamically stable with respect to the target structure at a folding temperature T-F approximate to T-Z. This 'cumulant design method' is based on a mean-field high temperature expansion of the molecular partition function. Folding simulations of the designed sequences confirm that sequences designed at T-Z do indeed fold optimally when T-F approximate to T-Z.Conclusions: The cumulant method is highly successful in designing model proteins, It also provides some insight into the thermal properties of real proteins, illuminating the features that distinguish thermostable and psychrotropic (cold-loving) sequences from their mesophilic counterparts. (C) Current Biology Ltd