SC20 Proceedings

The International Conference for High Performance Computing, Networking, Storage, and Analysis

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

Authors: Lorenzo Casalino, Abigail Dommer, Zied Gaieb, Emilia P. Barros, Terra Stzain, and Surl-Hee Ahn (University of California, San Diego); Anda Trifan (University of Illinois); Alexander Brace (Argonne National Laboratory (ANL)); Anthony Bogetti (University of Pittsburgh); Heng Ma (Argonne National Laboratory (ANL)); Hyungro Lee and Matteo Turilli (Rutgers University); Syma Khalid (University of Southampton); Lillian Chong (University of Pittsburgh); Carlos Simmerling (Stony Brook University); David Hardy, Julio Maia, and James Phillips (University of Illinois); Thorsten Kurth and Abraham Stern (Nvidia Corporation); Lei Huang and John McCalpin (University of Texas); Mahidhar Tatineni (San Diego Supercomputer Center); Tom Gibbs (Nvidia Corporation); John Stone (University of Illinois); Shantenu Jha (Brookhaven National Laboratory); Arvind Ramanathan (Argonne National Laboratory (ANL)); and Rommie E Amaro (University of California, San Diego)

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.

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