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SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome.

SARS-CoV-2 has intricate mechanisms for initiating infection, immune evasion/suppression and replication that depend on the structure and dynamics of its constituent proteins. Many protein structures have been solved, but far less is known about their relevant conformational changes. To address this challenge, over a million citizen scientists banded together through the Folding@home distributed computing project to create the first exascale computer and simulate 0.1 seconds of the viral proteome. Our adaptive sampling simulations predict dramatic opening of the apo spike complex, far beyond that seen experimentally, explaining and predicting the existence of 'cryptic' epitopes. Different spike variants modulate the probabilities of open versus closed structures, balancing receptor binding and immune evasion. We also discover dramatic conformational changes across the proteome, which reveal over 50 'cryptic' pockets that expand targeting options for the design of antivirals. All data a

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SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Zimmerman MI, Porter JR, Ward MD, Singh S, Vithani N, Meller A, Mallimadugula UL, Kuhn CE, Borowsky JH, Wiewiora RP, Hurley MFD, Harbison AM, Fogarty CA, Coffland JE, Fadda E, Voelz VA, Chodera JD, Bowman GR. (2021). SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome. Nature chemistry. PMID 34031561 · PMC8249329 · DOI 10.1038/s41557-021-00707-0
  • 证据类型：PRIMARY_RESEARCH
  • 主题：proteomics
  • 被引次数（采集时）：254
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/34031561)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    SARS-CoV-2 has intricate mechanisms for initiating infection, immune evasion/suppression and replication that depend on the structure and dynamics of its constituent proteins. Many protein structures have been solved, but far less is known about their relevant conformational changes. To address this challenge, over a million citizen scientists banded together through the Folding@home distributed computing project to create the first exascale computer and simulate 0.1 seconds of the viral proteome. Our adaptive sampling simulations predict dramatic opening of the apo spike complex, far beyond that seen experimentally, explaining and predicting the existence of 'cryptic' epitopes. Different spike variants modulate the probabilities of open versus closed structures, balancing receptor binding and immune evasion. We also discover dramatic conformational changes across the proteome, which reveal over 50 'cryptic' pockets that expand targeting options for the design of antivirals. All data and models are freely available online, providing a quantitative structural atlas.

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    SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome. · GeniOmics