Systematic modeling of SARS-CoV-2 protein structures

O'Donoghue, S. I.; Schafferhans, A.; Sikta, N.; Stolte, C.; Kaur, S.; Ho, B.; Anderson, S.; Procter, J. B.; Adcock, M.; Dallago, C.; Bordin, N.; Rost, B.

doi:10.1101/2020.07.16.207308

bioRxiv · 10.1101/2020.07.16.207308

Systematic modeling of SARS-CoV-2 protein structures

O'Donoghue, S. I.·Schafferhans, A.·Sikta, N.·Stolte, C.·Kaur, S.·Ho, B.·Anderson, S.·Procter, J. B.·Adcock, M.·Dallago, C.·Bordin, N.·Rost, B.

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Abstract

In response to the COVID-19 pandemic, many life scientists are focused on SARS-CoV-2. To help them use available structural data, we systematically modeled all viral proteins using all related 3D structures, generating 872 models that provide detail not available elsewhere. To organise these models, we created a structural coverage map: a novel, one-stop visualization summarizing what is -- and is not -- known about the 3D structure of the viral proteome. The map highlights structural evidence for viral protein interactions, mimicry, and hijacking; it also helps researchers find 3D models of interest, which can then be mapped with UniProt, PredictProtein, or CATH features. The resulting Aquaria-COVID resource (https://aquaria.ws/covid) helps scientists understand molecular mechanisms underlying coronavirus infection. Based on insights gained using our resource, we propose mechanisms by which the virus may enter immune cells, sense the cell type, then switch focus from viral reproduction to disrupting host immune responses. SignificanceCurrently, much of the COVID-19 viral proteome has unknown molecular structure. To improve this, we generated [~]1,000 structural models, designed to capture multiple states for each viral protein. To organise these models, we created a structure coverage map: a novel, one-stop visualization summarizing what is -- and is not -- known about viral protein structure. We used these data to create an online resource, designed to help COVID-19 researchers gain insight into the key molecular processes that drive infection. Based on insights gained using our resource, we speculate that the virus may sense the type of cells it infects and, within certain cells, it may switch from reproduction to disruption of the immune system.

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O'Donoghue, S. I., Schafferhans, A., Sikta, N., Stolte, C., Kaur, S., Ho, B., Anderson, S., Procter, J. B., Adcock, M., Dallago, C., Bordin, N., Rost, B.. 2020-07-17. Systematic modeling of SARS-CoV-2 protein structures. https://doi.org/10.1101/2020.07.16.207308

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