Elucidating OASL-RNA Interactions: Structural and energetic insights into vault RNAs binding

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling Pub Date : 2025-05-08 DOI:10.1016/j.jmgm.2025.109071

Erick Bahena-Culhuac , Rodolfo Daniel Avila-Avilés , José Manuel Hernández-Hernández , Rodolfo Gamaliel Avila-Bonilla

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引用次数: 0

Abstract

Oligoadenylate synthetase-like (OASL) proteins play an essential role in the innate immune response by detecting RNA molecules and modulating antiviral signalling pathways. This study investigated the structural and functional dynamics of OASL in its interaction with endogenous vault RNAs (vtRNAs) through computational analyses, including molecular docking and molecular dynamics simulations. Predicted 3D structures of vtRNAs revealed key interactions within the positively charged RNA-binding groove of OASL, involving residues such as Arg45, Lys63, and Arg196. Among the vtRNAs analysed, vtRNA 1-1 exhibited the highest binding affinity and stability, inducing conformational changes in OASL consistent with canonical activation mechanisms. In contrast, vtRNA 1–2 and 1–3 demonstrated moderate interactions, while vtRNA 2-1 had minimal impact on OASL conformation. Our results underscore the critical role of guanine- and cytosine-enriched regions in mediating binding stability and specificity, as corroborated by MM/GBSA calculations. The study highlights the molecular determinants of OASL-vtRNA interactions, offering structural insights into the mechanisms of nucleic acid recognition.

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阐明OASL-RNA相互作用：拱顶rna结合的结构和能量见解

寡聚腺苷酸合成酶样（OASL）蛋白通过检测RNA分子和调节抗病毒信号通路在先天免疫反应中发挥重要作用。本研究通过分子对接和分子动力学模拟等计算分析，研究了OASL与内源性拱顶rna （vtRNAs）相互作用的结构和功能动力学。预测的vtrna三维结构揭示了OASL正电荷rna结合槽内的关键相互作用，涉及Arg45、Lys63和Arg196等残基。在所分析的vtRNA中，vtRNA 1-1表现出最高的结合亲和力和稳定性，诱导OASL构象变化符合典型激活机制。相反，vtRNA 1-2和1-3表现出适度的相互作用，而vtRNA 2-1对OASL构象的影响最小。我们的研究结果强调了鸟嘌呤和胞嘧啶富集区在介导结合稳定性和特异性方面的关键作用，正如MM/GBSA计算所证实的那样。该研究强调了OASL-vtRNA相互作用的分子决定因素，为核酸识别机制提供了结构见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of molecular graphics & modelling 生物-计算机：跨学科应用

CiteScore

5.50

自引率

6.90%

发文量

216

审稿时长

35 days

期刊介绍： The Journal of Molecular Graphics and Modelling is devoted to the publication of papers on the uses of computers in theoretical investigations of molecular structure, function, interaction, and design. The scope of the journal includes all aspects of molecular modeling and computational chemistry, including, for instance, the study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, structure-activity and structure-property relationships, database mining, and compound library design. As a primary research journal, JMGM seeks to bring new knowledge to the attention of our readers. As such, submissions to the journal need to not only report results, but must draw conclusions and explore implications of the work presented. Authors are strongly encouraged to bear this in mind when preparing manuscripts. Routine applications of standard modelling approaches, providing only very limited new scientific insight, will not meet our criteria for publication. Reproducibility of reported calculations is an important issue. Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. Routine applications of existing methods that do not lead to genuinely new insight will not be considered.