动力学和静电定义了SARS-CoV-2刺突蛋白受体结合域内的变抗药位点。

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
FEBS Letters Pub Date : 2021-02-01 Epub Date: 2021-01-31 DOI:10.1002/1873-3468.14038
Sayan Bhattacharjee, Rajanya Bhattacharyya, Jayati Sengupta
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引用次数: 10

摘要

SARS-CoV-2病毒的发病机制是通过位于病毒尖刺上的受体结合结构域(RBD)识别宿主细胞的血管紧张素转换酶2 (ACE2)受体启动的。在这里,我们利用分子动力学模拟,展示了在apo-和ACE2受体结合状态下RBD内的变构串扰,揭示了基于动力学的相关运动和静电能量扰动对这种串扰的贡献。在apo-RBD中,基于相关运动的变构主导着固有的远端通信,而静电能量扰动决定了RBD残基与ACE2结合后的有利的双向串扰。有趣的是,变构途径是由在密切相关的冠状病毒中进化保守的残基组成的,这表明了这种通信的生物学相关性及其作为药物开发靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dynamics and electrostatics define an allosteric druggable site within the receptor-binding domain of SARS-CoV-2 spike protein.

The pathogenesis of the SARS-CoV-2 virus initiates through recognition of the angiotensin-converting enzyme 2 (ACE2) receptor of the host cells by the receptor-binding domain (RBD) located at the spikes of the virus. Here, using molecular dynamics simulations, we have demonstrated the allosteric crosstalk within the RBD in the apo- and the ACE2 receptor-bound states, revealing the contribution of the dynamics-based correlated motions and the electrostatic energy perturbations to this crosstalk. While allostery, based on correlated motions, dominates inherent distal communication in the apo-RBD, the electrostatic energy perturbations determine favorable pairwise crosstalk within the RBD residues upon binding to ACE2. Interestingly, the allosteric path is composed of residues which are evolutionarily conserved within closely related coronaviruses, pointing toward the biological relevance of the communication and its potential as a target for drug development.

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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
6.60
自引率
2.90%
发文量
303
审稿时长
1 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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