TY - JOUR T1 - AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics JF - bioRxiv DO - 10.1101/2020.11.19.390187 SP - 2020.11.19.390187 AU - Lorenzo Casalino AU - Abigail Dommer AU - Zied Gaieb AU - Emilia P. Barros AU - Terra Sztain AU - Surl-Hee Ahn AU - Anda Trifan AU - Alexander Brace AU - Anthony Bogetti AU - Heng Ma AU - Hyungro Lee AU - Matteo Turilli AU - Syma Khalid AU - Lillian Chong AU - Carlos Simmerling AU - David J. Hardy AU - Julio D. C. Maia AU - James C. Phillips AU - Thorsten Kurth AU - Abraham Stern AU - Lei Huang AU - John McCalpin AU - Mahidhar Tatineni AU - Tom Gibbs AU - John E. Stone AU - Shantenu Jha AU - Arvind Ramanathan AU - Rommie E. Amaro Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/20/2020.11.19.390187.abstract N2 - 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. https://doi.org/finalDOICompeting Interest StatementThe authors have declared no competing interest. ER -