AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics

被引：91

作者：

Casalino, Lorenzo ^{[1
]}

Dommer, Abigail ^{[1
]}

Gaieb, Zied ^{[1
]}

Barros, Emilia P. ^{[1
]}

Sztain, Terra ^{[1
]}

Ahn, Surl-Hee ^{[1
]}

Trifan, Anda ^{[2
,3
]}

Brace, Alexander ^{[2
]}

Bogetti, Anthony ^{[4
]}

Ma, Heng ^{[2
,5
]}

Lee, Hyungro ^{[6
]}

Turilli, Matteo ^{[6
]}

Khalid, Syma ^{[8
]}

Chong, Lillian ^{[4
]}

Simmerling, Carlos ^{[9
]}

Hardy, David J. ^{[3
]}

Maia, Julio D. C. ^{[3
]}

Phillips, James C. ^{[3
]}

Kurth, Thorsten ^{[10
]}

Stern, Abraham ^{[10
]}

Huang, Lei ^{[11
]}

McCalpin, John ^{[11
]}

Tatineni, Mahidhar ^{[12
]}

Gibbs, Tom ^{[10
]}

Stone, John E. ^{[3
]}

Jha, Shantenu ^{[6
,7
]}

Ramanathan, Arvind ^{[2
]}

Amaro, Rommie E. ^{[1
]}

机构：

[1] Univ Calif San Diego, 3234 Urey Hall,MC-0340, La Jolla, CA 92093 USA

[2] Argonne Natl Lab, Lemont, IL 60439 USA

[3] Univ Illinois, Urbana, IL USA

[4] Univ Pittsburgh, Pittsburgh, PA USA

[5] Univ Chicago, Chicago, IL 60637 USA

[6] Rutgers State Univ, Piscataway, NJ USA

[7] Brookhaven Natl Lab, Upton, NY 11973 USA

[8] Univ Southampton, Southampton, Hants, England

[9] SUNY Stony Brook, Stony Brook, NY 11794 USA

[10] NVIDIA Corp, Santa Clara, CA USA

[11] Texas Adv Comp Ctr, Austin, TX USA

[12] San Diego Supercomp Ctr, La Jolla, CA USA

来源：

INTERNATIONAL JOURNAL OF HIGH PERFORMANCE COMPUTING APPLICATIONS | 2021年 / 35卷 / 05期

关键词：

Molecular dynamics; deep learning; multiscale simulation; weighted ensemble; computational virology; SARS-CoV-2; COVID19; HPC; GPU; AI; SCALABLE MOLECULAR-DYNAMICS;

D O I：

10.1177/10943420211006452

中图分类号：

TP3 [计算技术、计算机技术];

学科分类号：

0812 ;

摘要：

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.

引用

页码：432 / 451

页数：20

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