Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

View ORCID ProfileLorenzo Casalino, Abigail Dommer, Zied Gaieb, Emilia P. Barros, Terra Sztain, Surl-Hee Ahn, Anda Trifan, Alexander Brace, Anthony Bogetti, Heng Ma, Hyungro Lee, Matteo Turilli, View ORCID ProfileSyma Khalid, Lillian Chong, Carlos Simmerling, David J. Hardy, Julio D. C. Maia, James C. Phillips, Thorsten Kurth, Abraham Stern, Lei Huang, John McCalpin, Mahidhar Tatineni, Tom Gibbs, John E. Stone, Shantenu Jha, Arvind Ramanathan, Rommie E. Amaro
doi: https://doi.org/10.1101/2020.11.19.390187
Lorenzo Casalino
1University of California San Diego
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lorenzo Casalino
Abigail Dommer
1University of California San Diego
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zied Gaieb
1University of California San Diego
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emilia P. Barros
1University of California San Diego
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Terra Sztain
1University of California San Diego
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Surl-Hee Ahn
1University of California San Diego
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anda Trifan
2Argonne National Lab
3University of Illinois at Urbana-Champaign
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Brace
2Argonne National Lab
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony Bogetti
4University of Pittsburgh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heng Ma
2Argonne National Lab
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyungro Lee
5Rutgers University & Brookhaven National Lab
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matteo Turilli
5Rutgers University & Brookhaven National Lab
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Syma Khalid
6University of Southampton
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Syma Khalid
Lillian Chong
4University of Pittsburgh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos Simmerling
7Stony Brook University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David J. Hardy
3University of Illinois at Urbana-Champaign
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julio D. C. Maia
3University of Illinois at Urbana-Champaign
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James C. Phillips
3University of Illinois at Urbana-Champaign
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thorsten Kurth
8NVIDIA Corporation
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abraham Stern
8NVIDIA Corporation
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lei Huang
9Texas Advanced Computing Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John McCalpin
9Texas Advanced Computing Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mahidhar Tatineni
10San Diego Supercomputing Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tom Gibbs
8NVIDIA Corporation
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John E. Stone
3University of Illinois at Urbana-Champaign
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shantenu Jha
5Rutgers University & Brookhaven National Lab
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arvind Ramanathan
2Argonne National Lab
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rommie E. Amaro
1University of California San Diego
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ramaro@ucsd.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

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. https://doi.org/finalDOI

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† Joint first authors

  • ↵∗ Contact authors: ramaro{at}ucsd.edu, ramanathana{at}anl.gov

  • Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from permissions{at}acm.org.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted November 20, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics
Lorenzo Casalino, Abigail Dommer, Zied Gaieb, Emilia P. Barros, Terra Sztain, Surl-Hee Ahn, Anda Trifan, Alexander Brace, Anthony Bogetti, Heng Ma, Hyungro Lee, Matteo Turilli, Syma Khalid, Lillian Chong, Carlos Simmerling, David J. Hardy, Julio D. C. Maia, James C. Phillips, Thorsten Kurth, Abraham Stern, Lei Huang, John McCalpin, Mahidhar Tatineni, Tom Gibbs, John E. Stone, Shantenu Jha, Arvind Ramanathan, Rommie E. Amaro
bioRxiv 2020.11.19.390187; doi: https://doi.org/10.1101/2020.11.19.390187
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics
Lorenzo Casalino, Abigail Dommer, Zied Gaieb, Emilia P. Barros, Terra Sztain, Surl-Hee Ahn, Anda Trifan, Alexander Brace, Anthony Bogetti, Heng Ma, Hyungro Lee, Matteo Turilli, Syma Khalid, Lillian Chong, Carlos Simmerling, David J. Hardy, Julio D. C. Maia, James C. Phillips, Thorsten Kurth, Abraham Stern, Lei Huang, John McCalpin, Mahidhar Tatineni, Tom Gibbs, John E. Stone, Shantenu Jha, Arvind Ramanathan, Rommie E. Amaro
bioRxiv 2020.11.19.390187; doi: https://doi.org/10.1101/2020.11.19.390187

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biophysics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8768)
  • Bioengineering (6481)
  • Bioinformatics (23348)
  • Biophysics (11752)
  • Cancer Biology (9150)
  • Cell Biology (13256)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11371)
  • Epidemiology (2066)
  • Evolutionary Biology (15091)
  • Genetics (10402)
  • Genomics (14012)
  • Immunology (9122)
  • Microbiology (22050)
  • Molecular Biology (8780)
  • Neuroscience (47381)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3705)
  • Plant Biology (8054)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2209)
  • Systems Biology (6016)
  • Zoology (1250)