Yin Shuangye, Ding Feng, Dokholyan Nikolay V
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Structure. 2007 Dec;15(12):1567-76. doi: 10.1016/j.str.2007.09.024.
In designing mutagenesis experiments, it is often crucial to know how certain mutations will affect the structure and thermodynamic stability of the protein. Here, we present a methodology, Eris, to efficiently and accurately compute the stability changes of proteins upon mutations using our protein-modeling suite, Medusa. We evaluate the stability changes upon mutations for 595 mutants from five structurally unrelated proteins, and find significant correlations between the predicted and experimental results. For cases when the high-resolution protein structure is not available, we find that better predictions are obtained by backbone structure prerelaxation. The advantage of our approach is that it is based on physical descriptions of atomic interactions, and does not rely on parameter training with available experimental protein stability data. Unlike other methods, Eris also models the backbone flexibility, thereby allowing for determination of the mutation-induced backbone conformational changes. Eris is freely available via the web server at http://eris.dokhlab.org.
在设计诱变实验时，了解某些突变如何影响蛋白质的结构和热力学稳定性通常至关重要。在此，我们提出了一种名为Eris的方法，利用我们的蛋白质建模套件Medusa高效且准确地计算蛋白质突变后的稳定性变化。我们评估了来自五种结构不相关蛋白质的595个突变体的突变后稳定性变化，并发现预测结果与实验结果之间存在显著相关性。对于无法获得高分辨率蛋白质结构的情况，我们发现通过主链结构预松弛可以获得更好的预测。我们方法的优势在于它基于原子相互作用的物理描述，并且不依赖于利用现有的实验蛋白质稳定性数据进行参数训练。与其他方法不同，Eris还对主链柔性进行建模，从而能够确定突变引起的主链构象变化。可通过网页服务器http://eris.dokhlab.org免费获取Eris。
