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.

中文翻译：

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信息理论方法，用于量化固有无序蛋白的序列-集合关系。

本质上无序的蛋白质（IDP）有助于多种功能。IDP的从头设计应为调节由这些系统控制的功能和表型打开方便之门。最近的设计工作集中在成分偏倚和特定的序列模式作为设计特征。对这些设计对序列-功能关系的影响的分析表明，单个序列/组成参数不足以描述IDP中的序列-功能关系。为了解决这个问题，我们已经为IDP的序列集成关系（SER）开发了信息理论方法。这些措施依赖于从所有原子模拟中得出的统计上强大的构象集合的先验可用性。我们表明，即使序列保守性很差，我们已经开发出的方法也可用于比较序列-集合关系。根据我们的结果，我们建议IDP的从头设计在其SER知识的指导下，应提供对它们的序列-集合-功能关系的更深入的了解。