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

2021 ◽  
pp. 109434202110064
Author(s):  
Lorenzo Casalino ◽  
Abigail C Dommer ◽  
Zied Gaieb ◽  
Emilia P Barros ◽  
Terra Sztain ◽  
...  
Keyword(s):  
Viral Envelope ◽  
Future Application ◽  
Conformational Sampling ◽  
Multiscale Simulations ◽  
Complex Environments ◽  
Molecular Systems ◽  
Strong Scaling ◽  
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 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.

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

2020 ◽  
Author(s):  
Lorenzo Casalino ◽  
Abigail Dommer ◽  
Zied Gaieb ◽  
Emilia P. Barros ◽  
Terra Sztain ◽  
...  
Keyword(s):  
New York ◽  
High Performance ◽  
Viral Envelope ◽  
Future Application ◽  
Conformational Sampling ◽  
Multiscale Simulations ◽  
Molecular Systems ◽  
Strong Scaling ◽  
Reference Format ◽  
Spike Dynamics

ABSTRACTWe 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 FormatLorenzo 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

scholarly journals Role of N-Linked Glycans in the Functions of Hepatitis C Virus Envelope Glycoproteins

2005 ◽  
Vol 79 (13) ◽  
pp. 8400-8409 ◽  
Author(s):  
Anne Goffard ◽  
Nathalie Callens ◽  
Birke Bartosch ◽  
Czeslaw Wychowski ◽  
François-Loïc Cosset ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Glycosylation Site ◽  
Viral Envelope ◽  
Envelope Glycoproteins ◽  
Wild Type ◽  
Virus Envelope ◽  
Glycosylation Sites

ABSTRACT Hepatitis C virus (HCV) encodes two viral envelope glycoproteins. E1 contains 4 or 5 N-linked glycosylation sites and E2 contains up to 11, with most of the sites being well conserved, suggesting that they play an essential role in some functions of these proteins. For this study, we used retroviral pseudotyped particles harboring mutated HCV envelope glycoproteins to study these glycans. The mutants were named with an N followed by a number related to the relative position of the potential glycosylation site in each glycoprotein (E1N1 to E1N4 for E1 mutants and E2N1 to E2N11 for E2 mutants). The characterization of these mutants allowed us to define three phenotypes. For the first group (E1N3, E2N3, E2N5, E2N6, E2N7, and E2N9), the infectivities of the mutants were close to that of the wild type. The second group (E1N1, E1N2, E1N4, E2N1, and E2N11) contained mutants that were still infectious but whose infectivities were reduced to <50% that of the wild type. The third group (E2N2, E2N4, E2N8, and E2N10) contained mutants that had almost totally lost infectivity. The absence of infectivity of the E2N8 and E2N10 mutants was due to the lack of incorporation of the E1E2 heterodimer into HCVpp, which was due to misfolding of the heterodimer, as shown by immunoprecipitation with conformation-sensitive antibodies and by a CD81 pull-down assay. The absence of infectivity of the E2N2 and E2N4 mutants indicated that these two glycans are involved in controlling HCV entry. Altogether, the data indicate that some glycans of HCV envelope glycoproteins play a major role in protein folding and others play a role in HCV entry.

Digital x-ray mapping of nanometer-size supported bimetallic catalysts

1988 ◽  
Vol 46 ◽  
pp. 530-531
Author(s):  
L. T. Germinario
Keyword(s):  
Background Radiation ◽  
Metal Cluster ◽  
Single Element ◽  
Beam Diameter ◽  
X Rays ◽  
X Ray ◽  
Major Interest ◽  
Induced Changes

Understanding the role of metal cluster composition in determining catalytic selectivity and activity is of major interest in heterogeneous catalysis. The electron microscope is well established as a powerful tool for ultrastructural and compositional characterization of support and catalyst. Because the spatial resolution of x-ray microanalysis is defined by the smallest beam diameter into which the required number of electrons can be focused, the dedicated STEM with FEG is the instrument of choice. The main sources of errors in energy dispersive x-ray analysis (EDS) are: (1) beam-induced changes in specimen composition, (2) specimen drift, (3) instrumental factors which produce background radiation, and (4) basic statistical limitations which result in the detection of a finite number of x-ray photons. Digital beam techniques have been described for supported single-element metal clusters with spatial resolutions of about 10 nm. However, the detection of spurious characteristic x-rays away from catalyst particles produced images requiring several image processing steps.

Consideraciones en torno a la reducción solipsista

1970 ◽  
Vol 11 ◽  
Author(s):  
Natalia Carolina Petrillo

ResumenEn el presente trabajo se intentará mostrar que la fenomenología no conduce a una postura solipsista. Para ello, se caracterizará en qué consiste el solipsismo. Luego, se intentará refutar a lo que se ha de llamar “solipsismo metafísico” y “solipsismo gnoseológico”, con el objetivo principal de poner de manifiesto el fundamento de motivación para la salida de la ficción solipsista.Palabras claves:Phenomenology – solipsim – empatía - HusserlAbstractWith the aim of showing that phenomenology does not lead in solipsism, I will first attempt a characterization of it. Then, I will attempt a refutation of the so-called “metaphysical” and “epistemological” solipsisms. Finally, the nature and role of Husserl´s solipsistic fiction is examined, and the grounds that motivate the overcoming of this standpoint are disclosed.key wordsFenomenología – solipsismo - empathy – Husserl

ART STUDIOS – A WAY TO DEVELOPE CHILDREN’S IMAGINATION

2020 ◽  
Vol 11 (1) ◽  
pp. 144-148
Author(s):  
Liuba Zlatkova ◽  
Keyword(s):  
Fairy Tale ◽  
Psychological Effects ◽  
Complete Product ◽  
The Arts ◽  
The Creation ◽  
Role Of Parents

The report describes the steps for creating a musical tale by children in the art studios of „Art Workshop“, Shumen. These studios are led by students volunteers related to the arts from pedagogical department of Shumen University, and are realized in time for optional activities in the school where the child studies. The stages of creating a complete product with the help of different arts are traced – from the birth of the idea; the creation of a fairy tale plot by the children; the characterization of the fairy-tale characters; dressing them in movement, song and speech; creating sets and costumes and creating a finished product to present on stage. The role of parents as a link and a necessary helper for children and leaders is also considered, as well as the positive psychological effects that this cooperation creates.

Conceptual Analysis Rebooted

2017 ◽  
Author(s):  
Edouard Machery
Keyword(s):  
Experimental Method ◽  
Conceptual Analysis ◽  
Philosophical Tradition ◽  
Traditional Use ◽  
Philosophical Significance ◽  
Conceptual Engineering ◽  
Method Of Cases

Chapter 7 proposes a new, naturalistic characterization of conceptual analysis, defends its philosophical significance, and shows that usual concerns with conceptual analysis do not apply to this revamped version. So understood, conceptual analysis encompasses both a descriptive project and a normative project, similar to explication or to conceptual engineering. Chapter 7 also defends the philosophical significance of this novel form of conceptual analysis and its continuity with the role of conceptual analysis in the philosophical tradition. Furthermore, naturalized conceptual analysis often requires empirical tools to be pursued successfully, and an experimental method of cases 2.0 should often replace the traditional use of cases in philosophy.

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