Department of Biomedical Engineering and Center for Science & Engineering of Living Systems (CSELS) Washington University in St. Louis, One Brookings Drive, Campus Box 1097, St. Louis MO, USA.
Protein Eng Des Sel. 2019 Dec 31;32(4):191-202. doi: 10.1093/protein/gzz014.
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.
无规卷曲蛋白质（IDPs）在许多功能中发挥作用。IDPs 的从头设计应该为调节这些系统控制的功能和表型开辟道路。最近的设计工作集中在组成偏倚和特定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 IDPs 中的序列-功能关系。为了解决这个问题，我们开发了用于 IDP 序列-集合关系（SERs）的信息论度量。这些措施依赖于从全原子模拟中得出的统计上稳健的构象集合的预先可用性。我们表明，即使序列保存不佳，我们开发的度量标准也可用于比较序列-集合关系。基于我们的结果，我们提出了由其 SER 指导的 IDPs 的从头设计，应该为深入了解其序列-集合-功能关系提供更好的见解。
