Rules of Physical Mathematics Govern Intrinsically Disordered Proteins.

Rules of Physical Mathematics Govern Intrinsically Disordered Proteins.
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DOI:
10.1146/annurev-biophys-120221-095357
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发表时间:
2022-05-09
影响因子:
12.4
通讯作者:
Haider, Austin
Haider, Austin
中科院分区:
生物学1区
文献类型:
--
作者:
Ghosh, Kingshuk;Huihui, Jonathan;Phillips, Michael;Haider, Austin

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与具有独特折叠状态的可折叠蛋白质形成鲜明对比的是,固有无序蛋白质和区域(IDP)以永久无序的集合存在。然而,一个IDP合奏的构象特征,即使是平均的,这是特定于其序列。事实上,IDP序列的细微变化可以调节其构象特征和功能。理论物理学的最新进展揭示了一组优雅的数学表达式,描述了IDP序列之间的复杂关系,它们的整体构象,以及它们的生物功能的调节。这些方程还描述了IDP序列的分子特性,预测其功能的相似性和差异性,并促进序列的功能分类,这是传统生物信息学尚未解决的挑战。这些物理序列模式化指标为推进合成生物学提供了一个有前途的新途径,此时,由IDP介导的多种新型功能模式正在出现。
In stark contrast to foldable proteins with a unique folded state, intrinsically disordered proteins and regions (IDPs) persist in perpetually disordered ensembles. Yet an IDP ensemble has conformational features—even when averaged—that are specific to its sequence. In fact, subtle changes in an IDP sequence can modulate its conformational features and its function. Recent advances in theoretical physics reveal a set of elegant mathematical expressions that describe the intricate relationships among IDP sequences, their ensemble conformations, and the regulation of their biological functions. These equations also describe the molecular properties of IDP sequences that predict similarities and dissimilarities in their functions and facilitate classification of sequences by function, an unmet challenge to traditional bioinformatics. These physical sequence-patterning metrics offer a promising new avenue for advancing synthetic biology at a time when multiple novel functional modes mediated by IDPs are emerging.
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