Cargando…
AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics
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 en...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064023/ http://dx.doi.org/10.1177/10943420211006452 |
_version_ | 1783682047497207808 |
---|---|
author | Casalino, Lorenzo Dommer, Abigail C Gaieb, Zied Barros, Emilia P Sztain, Terra Ahn, Surl-Hee Trifan, Anda Brace, Alexander Bogetti, Anthony T Clyde, Austin Ma, Heng Lee, Hyungro Turilli, Matteo Khalid, Syma Chong, Lillian T Simmerling, Carlos Hardy, David J Maia, Julio DC Phillips, James C Kurth, Thorsten Stern, Abraham C Huang, Lei McCalpin, John D Tatineni, Mahidhar Gibbs, Tom Stone, John E Jha, Shantenu Ramanathan, Arvind Amaro, Rommie E |
author_facet | Casalino, Lorenzo Dommer, Abigail C Gaieb, Zied Barros, Emilia P Sztain, Terra Ahn, Surl-Hee Trifan, Anda Brace, Alexander Bogetti, Anthony T Clyde, Austin Ma, Heng Lee, Hyungro Turilli, Matteo Khalid, Syma Chong, Lillian T Simmerling, Carlos Hardy, David J Maia, Julio DC Phillips, James C Kurth, Thorsten Stern, Abraham C Huang, Lei McCalpin, John D Tatineni, Mahidhar Gibbs, Tom Stone, John E Jha, Shantenu Ramanathan, Arvind Amaro, Rommie E |
author_sort | Casalino, Lorenzo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8064023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-80640232021-04-26 AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics Casalino, Lorenzo Dommer, Abigail C Gaieb, Zied Barros, Emilia P Sztain, Terra Ahn, Surl-Hee Trifan, Anda Brace, Alexander Bogetti, Anthony T Clyde, Austin Ma, Heng Lee, Hyungro Turilli, Matteo Khalid, Syma Chong, Lillian T Simmerling, Carlos Hardy, David J Maia, Julio DC Phillips, James C Kurth, Thorsten Stern, Abraham C Huang, Lei McCalpin, John D Tatineni, Mahidhar Gibbs, Tom Stone, John E Jha, Shantenu Ramanathan, Arvind Amaro, Rommie E Int J High Perform Comput Appl Special Issue Papers 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. SAGE Publications 2021-09 /pmc/articles/PMC8064023/ http://dx.doi.org/10.1177/10943420211006452 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Special Issue Papers Casalino, Lorenzo Dommer, Abigail C Gaieb, Zied Barros, Emilia P Sztain, Terra Ahn, Surl-Hee Trifan, Anda Brace, Alexander Bogetti, Anthony T Clyde, Austin Ma, Heng Lee, Hyungro Turilli, Matteo Khalid, Syma Chong, Lillian T Simmerling, Carlos Hardy, David J Maia, Julio DC Phillips, James C Kurth, Thorsten Stern, Abraham C Huang, Lei McCalpin, John D Tatineni, Mahidhar Gibbs, Tom Stone, John E Jha, Shantenu Ramanathan, Arvind Amaro, Rommie E AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics |
title | AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics |
title_full | AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics |
title_fullStr | AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics |
title_full_unstemmed | AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics |
title_short | AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics |
title_sort | ai-driven multiscale simulations illuminate mechanisms of sars-cov-2 spike dynamics |
topic | Special Issue Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064023/ http://dx.doi.org/10.1177/10943420211006452 |
work_keys_str_mv | AT casalinolorenzo aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT dommerabigailc aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT gaiebzied aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT barrosemiliap aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT sztainterra aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT ahnsurlhee aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT trifananda aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT bracealexander aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT bogettianthonyt aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT clydeaustin aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT maheng aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT leehyungro aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT turillimatteo aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT khalidsyma aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT chonglilliant aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT simmerlingcarlos aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT hardydavidj aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT maiajuliodc aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT phillipsjamesc aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT kurththorsten aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT sternabrahamc aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT huanglei aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT mccalpinjohnd aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT tatinenimahidhar aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT gibbstom aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT stonejohne aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT jhashantenu aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT ramanathanarvind aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics AT amarorommiee aidrivenmultiscalesimulationsilluminatemechanismsofsarscov2spikedynamics |