AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics

  1. Lorenzo Casalino
  2. Abigail Dommer
  3. Zied Gaieb
  4. Emilia P. Barros
  5. Terra Sztain
  6. Surl-Hee Ahn
  7. Anda Trifan
  8. Alexander Brace
  9. Anthony Bogetti
  10. Heng Ma
  11. Hyungro Lee
  12. Matteo Turilli
  13. Syma Khalid
  14. Lillian Chong
  15. Carlos Simmerling
  16. David J. Hardy
  17. Julio D. C. Maia
  18. James C. Phillips
  19. Thorsten Kurth
  20. Abraham Stern
  21. Lei Huang
  22. John McCalpin
  23. Mahidhar Tatineni
  24. Tom Gibbs
  25. John E. Stone
  26. Shantenu Jha
  27. Arvind Ramanathan
  28. Rommie E. Amaro
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Abstract

We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike’s full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems.

ACM Reference Format

Lorenzo Casalino1†, Abigail Dommer1†, Zied Gaieb1†, Emilia P. Barros1, Terra Sztain1, Surl-Hee Ahn1, Anda Trifan2,3, Alexander Brace2, Anthony Bogetti4, Heng Ma2, Hyungro Lee5, Matteo Turilli5, Syma Khalid6, Lillian Chong4, Carlos Simmerling7, David J. Hardy3, Julio D. C. Maia3, James C. Phillips3, Thorsten Kurth8, Abraham Stern8, Lei Huang9, John McCalpin9, Mahidhar Tatineni10, Tom Gibbs8, John E. Stone3, Shantenu Jha5, Arvind Ramanathan2∗, Rommie E. Amaro1∗. 2020. AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics. In Supercomputing ’20: International Conference for High Performance Computing, Networking, Storage, and Analysis. ACM, New York, NY, USA, 14 pages. <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://doi.org/finalDOI">https://doi.org/finalDOI</ext-link>

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