Department of Chemistry and Biochemistry and Department of Physics, University of California Santa Barbara, Santa Barbara, California 93106, USA.
Protein Sci. 2011 May;20(5):818-26. doi: 10.1002/pro.605. Epub 2011 Mar 30.
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.
我们使用最近开发的粗粒化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。我们的模拟结果为实验观察到的四螺旋束稳定性随序列长度增加而增加提供了一种可能的解释。具体来说，我们表明，仅由极性残基组成的短序列和通过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了重要作用。最后，我们提出了一个额外的突变，挽救了一个原本会采取紧凑错误折叠状态的短氨基酸序列。我们的工作表明，简单的计算模型可以作为从头设计蛋白质过程中的一种补充工具。
