Thread by @Mizimmer90

I'm excited to share that our work on SARS-CoV-2 is now published in @NatureChemistry! I'm humbled to have led this effort and provide a brief summary below: nature.com/articles/s4155…

Millions of @foldingathome users pooled their resources to create the first #Exascale computer and generated the world's largest MD dataset, simulating nearly the entire SARS-CoV-2 proteome.

We were the first group to discover that the Spike protein has incredible conformational heterogeneity and can adopt an 'open' state that reveals many cryptic epitopes. Many nAbs have since been found to target these cryptic epitopes!

With our immense simulations, we were able to characterize this opening with full atomic detail!

The population of the open state is not conserved among variants. Mutations on the Spike can modulate its propensity to open, likely impacting pathogenicity and efficacy of immune evasion.

Additionally, we have simulated nearly the entire proteome and documented over 50 new and novel cryptic pockets. Any of these pockets might lead to the development of potent antivirals, which are still needed to prevent severe COVID and deaths.

All of our datasets are publicly available! You can download fully constructed Markov models at: osf.io/fs2yv/ and raw simulations from our partners @MolSSI_NSF

First and foremost, a huge thank you to each and every folder around the world! Without your quick response, this work would not have been possible! #CitizenScience

Another thank you to the many companies and research centers that have contributed resources to aid in data collection and analysis. These resources were absolutely necessary for collection, storage, and analysis of the datasets!

To name a few: @Microsoft #AIforHealth, @Avast, @Oracle, @VMware, @NVIDIA, @LinusTech, @PCMR, @awscloud, @cisco, @amd, @PureStorage, @UKRI_News, @Seagate, @intel, @arm, @a16z, @Github, @DataDog, @GIGABYTEUSA, @NSF, @NIH, @CERN, and @Dell

Thank you to each of the co-authors who worked so hard to overcome the challenges of generating and curating this data! @Mickdub29, @sukritsingh92, @VithaniNeha, @upasanalm, @catherine_kuhnn, @rafwiewiora, @llabrword, @A_Harbison_, @2016Carl, @jcoffland

Also a big thanks to each of the PIs! @ElisaTelisa, @voelzlab, @jchodera, @drGregBowman

And I conclude with my favorite movie of the spike opening!