Relative stability of de novo four-helix bundle proteins: Insights from coarse grained molecular simulations
Relative stability of de novo four-helix bundle proteins: Insights from coarse grained molecular simulations
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DOI：
10.1002/pro.605
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发表时间：
2011-05-01
期刊：
影响因子：
8
通讯作者：
Shea, Joan-Emma
中科院分区：
文献类型：
--
作者：
Bellesia, Giovanni;Jewett, Andrew I.;Shea, Joan-Emma
我们使用最近开发的粗粒度计算模型来研究两组不同的从头设计的四螺旋束蛋白的相对稳定性。我们的模拟为实验观察到的四螺旋束稳定性随着序列长度的增加而增加提供了可能的解释。详细而言，我们表明仅由极性残基组成的短子序列和通过特定位置的不同点突变插入的额外非极性残基似乎在稳定较长序列中的四螺旋束构象方面发挥着重要作用。最后，我们提出了一个额外的突变，可以挽救一个短氨基酸序列，否则该序列将采用紧凑的错误折叠状态。我们的工作表明，简单的计算模型可以用作从头蛋白质设计过程中的补充工具。
We use a recently developed coarse-grained computational model to investigate the relative stability of two different sets of de novo designed four-helix bundle proteins. Our simulations suggest a possible explanation for the experimentally observed increase in stability of the four-helix bundles with increasing sequence length. In details, we show that both short subsequences composed only by polar residues and additional nonpolar residues inserted, via different point mutations in ad hoc positions, seem to play a significant role in stabilizing the four-helix bundle conformation in the longer sequences. Finally, we propose an additional mutation that rescues a short amino acid sequence that would otherwise adopt a compact misfolded state. Our work suggests that simple computational models can be used as a complementary tool in the design process of de novo proteins.