Undersampling and the inference of coevolution in proteins.
Undersampling and the inference of coevolution in proteins.
复制标题
欠采样和蛋白质共同进化的推断。
DOI：
10.1016/j.cels.2022.12.013
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发表时间：
2023
期刊：
影响因子：
9.3
通讯作者：
Ranganathan,Rama
中科院分区：
文献类型：
--
作者：
Kleeorin,Yaakov;Russ,WilliamP;Rivoire,Olivier;Ranganathan,Rama
蛋白质的结构、功能和进化依赖于氨基酸之间的局部和集体上位性相互作用。定义这些相互作用的一种有效方法是构建氨基酸之间偶联的模型，该模型重现在组成蛋白质家族的序列中观察到的经验统计(频率和相关性)。然后对顶部联轴器进行解释。在这里，我们表明，正如目前实施的那样，这一推断不等同地代表了上位性相互作用，这个问题从根本上是由于在蛋白质中发生上位性作用的不同规模的序列的有限采样引起的。我们表明，这些问题解释了目前方法预测氨基酸之间三级接触的能力，以及无法明显地暴露功能相关的、集体进化的称为扇区的更大的残基网络。这项工作为更深入地理解和改进基于进化的蛋白质模型提供了必要的基础。
Protein structure, function, and evolution depend on local and collective epistatic interactions between amino acids. A powerful approach to defining these interactions is to construct models of couplings between amino acids that reproduce the empirical statistics (frequencies and correlations) observed in sequences comprising a protein family. The top couplings are then interpreted. Here, we show that as currently implemented, this inference unequally represents epistatic interactions, a problem that fundamentally arises from limited sampling of sequences in the context of distinct scales at which epistasis occurs in proteins. We show that these issues explain the ability of current approaches to predict tertiary contacts between amino acids and the inability to obviously expose larger networks of functionally relevant, collectively evolving residues called sectors. This work provides a necessary foundation for more deeply understanding and improving evolution-based models of proteins.