Revealing the water-catalyzed activation of Chikungunya virus non-structural protein 2 (nsP2)

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling Pub Date : 2025-07-28 DOI:10.1016/j.jmgm.2025.109129

Emanuelly Karla Araújo Padilha , Júlio Cosme Santos da Silva , Edeildo Ferreira da Silva-Júnior

引用次数: 0

Abstract

– Chikungunya virus (CHIKV) poses a significant global health threat due to its association with debilitating arthritis and the limited therapeutic options available. Non-structural protein 2 (nsP2) is a multifunctional enzyme and cysteine protease that plays a critical role in viral replication, making it an attractive target for antiviral strategies. This study investigates the water-mediated catalytic activation mechanism of nsP2, with a particular emphasis on its catalytic role. Using density functional theory (DFT) calculations, our findings reveal that the water-mediated reaction significantly lowers the activation energy barrier. These insights provide a deeper understanding of the catalytic dynamics of nsP2, laying the groundwork for the design of inhibitors targeting this enzyme.

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揭示基孔肯雅病毒非结构蛋白2 （nsP2）的水催化活化

-基孔肯雅病毒（CHIKV）由于与衰弱性关节炎相关以及可用的治疗方案有限，对全球健康构成重大威胁。非结构蛋白2 （nsP2）是一种多功能酶和半胱氨酸蛋白酶，在病毒复制中起着关键作用，使其成为抗病毒策略的一个有吸引力的靶点。本研究探讨了nsP2的水催化活化机理，重点研究了其催化作用。利用密度泛函理论（DFT）计算，我们的研究结果表明，水介导的反应显著降低了活化能垒。这些见解提供了对nsP2催化动力学的更深入了解，为设计针对该酶的抑制剂奠定了基础。

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.