A substantial portion of various organisms’ proteomes comprises intrinsically disordered proteins (IDPs) that lack a defined three-dimensional structure. These IDPs exhibit a diverse array of conformations, displaying remarkable spatiotemporal heterogeneity and exceptional conformational flexibility. Characterizing the structure or structural ensemble of IDPs presents significant conceptual and methodological challenges owing to the absence of a well-defined native structure. While databases such as the Protein Ensemble Database (PED) provide IDP ensembles obtained through a combination of experimental data and molecular modeling, the absence of reaction coordinates poses challenges in comprehensively understanding pertinent aspects of the system. In this study, we leverage the energy landscape visualization method (JCTC, 6482, 2019) to scrutinize four IDP ensembles sourced from PED. ELViM, a methodology that circumvents the need for a priori reaction coordinates, aids in analyzing the ensembles. The specific IDP ensembles investigated are as follows: two fragments of nucleoporin (NUL: 884-993 and NUS: 1313-1390), yeast sic 1 N-terminal (1-90), and the N-terminal SH3 domain of Drk (1-59). Utilizing ELViM enables the comprehensive validation of ensembles, facilitating the detection of potential inconsistencies in the sampling process. Additionally, it allows for identifying and characterizing the most prevalent conformations within an ensemble. Moreover, ELViM facilitates the comparative analysis of ensembles obtained under diverse conditions, thereby providing a powerful tool for investigating the functional mechanisms of IDPs.

中文翻译：

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了解本质上无序的蛋白质整体的能量景观


各种生物体的蛋白质组的很大一部分由本质上无序的蛋白质（IDP）组成，缺乏明确的三维结构。这些 IDP 表现出多种构象，表现出显着的时空异质性和异常的构象灵活性。由于缺乏明确定义的本土结构，表征国内流离失所者的结构或结构整体提出了重大的概念和方法上的挑战。虽然蛋白质集成数据库 (PED) 等数据库提供了通过实验数据和分子建模相结合获得的 IDP 集成，但反应坐标的缺乏给全面理解系统的相关方面带来了挑战。在本研究中，我们利用能源景观可视化方法（JCTC，6482，2019）来仔细检查来自 PED 的四个 IDP 集合。 ELViM 是一种无需先验反应坐标的方法，有助于分析整体。研究的具体 IDP 整体如下：核孔蛋白的两个片段（NUL：884-993 和 NUS：1313-1390）、酵母 sic 1 N 端（1-90）和 Drk 的 N 端 SH3 结构域（1 -59）。利用 ELViM 可以对整体进行全面验证，从而有助于检测采样过程中潜在的不一致之处。此外，它还可以识别和表征整体中最普遍的构象。此外，ELViM 有助于对不同条件下获得的集合进行比较分析，从而为研究 IDP 的功能机制提供了强大的工具。