Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling

Weria Pezeshkian; Fabian Grünewald; Oleksandr Narykov; Senbao Lu; Valeria Arkhipova; Alexey Solodovnikov; Tsjerk A Wassenaar; Siewert J Marrink; Dmitry Korkin

doi:10.1016/j.str.2023.02.006

Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling

Structure. 2023 Apr 6;31(4):492-503.e7. doi: 10.1016/j.str.2023.02.006. Epub 2023 Mar 3.

Authors

Weria Pezeshkian¹, Fabian Grünewald², Oleksandr Narykov³, Senbao Lu⁴, Valeria Arkhipova⁵, Alexey Solodovnikov⁵, Tsjerk A Wassenaar⁶, Siewert J Marrink⁷, Dmitry Korkin⁸

Affiliations

¹ Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, 9747AG Groningen, the Netherlands; Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.
² Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, 9747AG Groningen, the Netherlands.
³ Department of Computer Science, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
⁴ Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
⁵ Science in Motion, Moscow 123458, Russia.
⁶ Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, 9747AG Groningen, the Netherlands; Institute for Life Science and Technology, Hanze University of Applied Sciences, 9747AS Groningen, the Netherlands.
⁷ Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, 9747AG Groningen, the Netherlands. Electronic address: s.j.marrink@rug.nl.
⁸ Department of Computer Science, Worcester Polytechnic Institute, Worcester, MA 01609, USA; Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA 01609, USA. Electronic address: korkin@korkinlab.org.

PMID: 36870335
DOI: 10.1016/j.str.2023.02.006

Abstract

Despite tremendous efforts, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. SARS-CoV-2 envelope is a key structural component of the virion that encapsulates viral RNA. It is composed of three structural proteins, spike, membrane (M), and envelope, which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multi-scale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns. These results are in good agreement with current experimental data, demonstrating a generic and versatile approach to model the structure of a virus de novo.

Keywords: M dimer; SARS-CoV-2 structure; betacoronavirus; coronavirus; envelope structure; integrative modeling; molecular dynamics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Molecular Dynamics Simulation
SARS-CoV-2*