Stability strengths and weaknesses in protein structures detected by statistical potentials: Application to bovine seminal ribonuclease
Stability strengths and weaknesses in protein structures detected by statistical potentials: Application to bovine seminal ribonuclease
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DOI：
10.1002/prot.24962
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发表时间：
2016-01-01
影响因子：
2.9
通讯作者：
Rooman, Marianne
中科院分区：
文献类型：
--
作者：
De Laet, Marie;Gilis, Dimitri;Rooman, Marianne
我们提出了一种电子方法来估计蛋白质中每个残基对其整体稳定性的贡献，使用三个数据库派生的统计势，这三个统计势分别基于残基间距离、骨架扭转角和溶剂可及性。对折叠自由能贡献非常不利的残基被定义为稳定性弱点，而表现出高度稳定贡献的残基被称为稳定性强度。空间接触残基上的优势和/或劣势被聚集成三维(3D)稳定性斑块。对蛋白质中包含强弱的区域的识别和分析可能揭示结构或功能特征，和/或引入突变的有趣的点。为了说明我们的方法的能力，我们将其应用于牛精液核糖核酸酶。这种酶催化RNA链的降解，在生理条件下具有进行3D结构域交换的特性。比较了单体、二聚体和互换二聚体的优缺点。我们发现了催化残基之间的弱点，以及三种形式的底物结合残基之间的弱点和优势的混合体。在涉及3D交换的区域中，我们观察到单体中的弱点积累，这些弱点在二聚体中消失，特别是在被交换的二聚体中。此外，发现单体同源蛋白在这些区域表现出较少的弱点，而已知的有利于非交换二聚的突变体似乎在这种形式下稳定下来。我们的方法对于功能注释、目标突变的合理预测以及构象重排时稳定性变化的映射有几个方面的前景。蛋白质2016；84：143-158。(C)2015年威利期刊公司。
We present an in silico method to estimate the contribution of each residue in a protein to its overall stability using three database-derived statistical potentials that are based on inter-residue distances, backbone torsion angles and solvent accessibility, respectively. Residues that contribute very unfavorably to the folding free energy are defined as stability weaknesses, whereas residues that show a highly stabilizing contribution are called stability strengths. Strengths and/or weaknesses on residues that are in spatial contact are clustered into 3-dimensional (3D) stability patches. The identification and analysis of strength- and weakness-containing regions in a protein may reveal structural or functional characteristics, and/or interesting spots to introduce mutations. To illustrate the power of our method, we apply it to bovine seminal ribonuclease. This enzyme catalyzes the degradation of RNA strands, and has the peculiarity of undergoing 3D domain swapping in physiological conditions. The weaknesses and strengths were compared among the monomeric, dimeric and swapped dimeric forms. We identified weaknesses among the catalytic residues and a mixture of weaknesses and strengths among the substrate-binding residues in the three forms. In the regions involved in 3D swapping, we observed an accumulation of weaknesses in the monomer, which disappear in the dimer and especially in the swapped dimer. Moreover, monomeric homologous proteins were found to exhibit less weaknesses in these regions, whereas mutants known to favor unswapped dimerization appear stabilized in this form. Our method has several perspectives for functional annotation, rational prediction of targeted mutations, and mapping of stability changes upon conformational rearrangements. Proteins 2016; 84:143-158. (c) 2015 Wiley Periodicals, Inc.