定量内在无序蛋白质序列集合关系的信息论方法

Megan C. Cohan, Kiersten M. Ruff, R. Pappu
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引用次数: 18

摘要

内在无序蛋白(IDPs)具有多种功能。IDPs的从头设计应该打开由这些系统控制的调节功能和表型的大门。最近的设计工作集中在组合偏差和特定序列模式作为设计特征。分析这些设计对序列-函数关系的影响表明,单个序列/组成参数不足以描述国内流离失所者的序列-函数关系。为了解决这一问题,我们开发了IDPs序列集成关系(SERs)的信息理论度量。这些措施依赖于从所有原子模拟中获得的统计上可靠的构象集合的先验可用性。我们表明,我们已经开发的措施是有用的比较序列-集成关系,甚至当序列保守性差。基于我们的研究结果,我们建议在SERs知识的指导下重新设计IDPs,应该提供对其序列-集成-函数关系的更好见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Information theoretic measures for quantifying sequence–ensemble relationships of intrinsically disordered proteins
Abstract Intrinsically disordered proteins (IDPs) contribute to a multitude of functions. De novo design of IDPs should open the door to modulating functions and phenotypes controlled by these systems. Recent design efforts have focused on compositional biases and specific sequence patterns as the design features. Analysis of the impact of these designs on sequence-function relationships indicates that individual sequence/compositional parameters are insufficient for describing sequence-function relationships in IDPs. To remedy this problem, we have developed information theoretic measures for sequence–ensemble relationships (SERs) of IDPs. These measures rely on prior availability of statistically robust conformational ensembles derived from all atom simulations. We show that the measures we have developed are useful for comparing sequence-ensemble relationships even when sequence is poorly conserved. Based on our results, we propose that de novo designs of IDPs, guided by knowledge of their SERs, should provide improved insights into their sequence–ensemble–function relationships.
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