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Are coarse-grained models apt to detect protein thermal stability? The case of OPEP force field.
Journal of Non-Crystalline Solids ( IF 3.5 ) Pub Date : 2014-07-22 , DOI: 10.1016/j.jnoncrysol.2014.07.005
Maria Kalimeri 1 , Philippe Derreumaux 2 , Fabio Sterpone 1
Affiliation  

We present the first investigation of the kinetic and thermodynamic stability of two homologous thermophilic and mesophilic proteins based on the coarse-grained model OPEP. The object of our investigation is a pair of G-domains of relatively large size, 200 amino acids each, with an experimental stability gap of about 40 K. The OPEP force field is able to maintain stable the fold of these relatively large proteins within the hundrend-nanosecond time scale without including external constraints. This makes possible to characterize the conformational landscape of the folded protein as well as to explore the unfolding. In agreement with all-atom simulations used as a reference, we show that the conformational landscape of the thermophilic protein is characterized by a larger number of substates with slower dynamics on the network of states and more resilient to temperature increase. Moreover, we verify the stability gap between the two proteins using replica-exchange simulations and estimate a difference between the melting temperatures of about 23 K, in fair agreement with experiment. The detailed investigation of the unfolding thermodynamics, allows to gain insight into the mechanism underlying the enhanced stability of the thermophile relating it to a smaller heat capacity of unfolding.

中文翻译:

粗粒度模型是否易于检测蛋白质热稳定性?OPEP力场案例。

我们首次研究了基于粗粒度模型 OPEP 的两种同源嗜热和嗜温蛋白的动力学和热力学稳定性。我们研究的对象是一对相对较大的 G 域,每个有 200 个氨基酸,实验稳定性差距约为 40 K。OPEP 力场能够保持这些相对较大的蛋白质在百纳秒时间尺度,不包括外部约束。这使得表征折叠蛋白质的构象景观以及探索展开成为可能。与用作参考的全原子模拟一致,我们表明,嗜热蛋白的构象景观的特点是有大量的亚状态,状态网络上的动力学较慢,对温度升高的抵抗力更强。此外,我们使用复制交换模拟验证了两种蛋白质之间的稳定性差距,并估计了约 23 K 的解链温度之间的差异,与实验完全一致。展开热力学的详细研究,可以深入了解嗜热菌稳定性增强的机制,并将其与较小的展开热容量相关联。与实验完全一致。展开热力学的详细研究,可以深入了解嗜热菌稳定性增强的机制,并将其与较小的展开热容量相关联。与实验完全一致。展开热力学的详细研究,可以深入了解嗜热菌稳定性增强的机制,并将其与较小的展开热容量相关联。
更新日期:2019-11-01
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