Intrinsically disordered proteins (IDPs) are crucial players in various cellular activities. Several experimental and computational analyses have been conducted to study structural pliability and functional potential of IDPs. In spite of active research in past few decades, what induces structural disorder in IDPs and how is still elusive. Many studies testify that sequential and spatial neighbours often play important roles in determining structural and functional behaviour of proteins. Considering this fact, we assessed sequence neighbours of intrinsically disordered regions (IDRs) to understand if they have any role to play in inducing structural flexibility in IDPs. Our analysis includes 97% eukaryotic IDPs and 3% from bacteria and viruses. Physicochemical and structural parameters including amino acid propensity, hydrophobicity, secondary structure propensity, relative solvent accessibility, B-factor and atomic packing density are used to characterise the neighbouring residues of IDRs (NRIs). We show that NRIs exhibit a unique nature, which makes them stand out from both ordered and disordered residues. They show correlative occurrences of residue pairs like Ser-Thr and Gln-Asn, indicating their tendency to avoid strong biases of order or disorder promoting amino acids. We also find differential preferences of amino acids between N- and C-terminal neighbours, which might indicate a plausible directional effect on the dynamics of adjacent IDRs. We designed an efficient prediction tool using Random Forest to distinguish the NRIs from the ordered residues. Our findings will contribute to understand the behaviour of IDPs, and may provide potential lead in deciphering the role of IDRs in protein folding and assembly.

中文翻译：

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本质上无序的区域的序列邻居是否促进本质上无序的蛋白质的结构柔性？

本质上无序的蛋白质（IDP）在各种细胞活动中起着至关重要的作用。已经进行了一些实验和计算分析来研究IDP的结构柔韧性和功能潜力。尽管在过去的几十年中进行了积极的研究，但是什么导致了国内流离失所者的结构紊乱，以及如何仍然难以捉摸。许多研究证明，顺序和空间邻居通常在确定蛋白质的结构和功能行为中起重要作用。考虑到这一事实，我们评估了内在无序区域（IDR）的序列邻居，以了解它们是否在诱导IDP中的结构灵活性方面发挥任何作用。我们的分析包括97％的真核IDP和3％的细菌和病毒。物理化学和结构参数，包括氨基酸倾向，疏水性，二级结构倾向，相对溶剂可及性，B因子和原子堆积密度用于表征IDR（NRI）的相邻残基。我们显示NRI展现出独特的性质，这使它们从有序和无序残基中脱颖而出。它们显示出相关残基对的出现，如Ser-Thr和Gln-Asn，表明它们倾向于避免强烈的顺序偏倚或促进氨基酸紊乱。我们还发现N端和C端邻居之间氨基酸的偏好不同，这可能表明对相邻IDR动力学的可能的方向性影响。我们使用随机森林设计了一种有效的预测工具，以将NRI与有序残基区分开。我们的发现将有助于理解国内流离失所者的行为，