Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane

Overview

Journal J Phys Chem B

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Jun 20

PMID 32559081

Citations 143

Authors

Hyeonuk Woo

Sang-Jun Park

Yeol Kyo Choi

Taeyong Park

Maham Tanveer

Yiwei Cao

Nathan R Kern

Jumin Lee

Min Sun Yeom

Tristan I Croll

Chaok Seok

Wonpil Im

Affiliations

Soon will be listed here.

Abstract

This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.

Citing Articles

Exploring the effects of N234 and N343 linked glycans to SARS CoV 2 spike protein pocket accessibility using Gaussian accelerated molecular dynamics simulations.

Cheng R, Lim J, Fortuna M, Reyes Jr D, Hans E, Nellas R Sci Rep. 2025; 15(1):7052.

PMID: 40016249 PMC: 11868416. DOI: 10.1038/s41598-025-85153-5.

Bioinformatic Selection of Mannose-Specific Lectins from as SARS-CoV-2 Inhibitors Analysing Protein-Protein Interaction.

Isakovic S, Sencanski M, Perovic V, Stevanovic K, Prodic I Life (Basel). 2025; 15(2).

PMID: 40003571 PMC: 11856470. DOI: 10.3390/life15020162.

Quantitative Prediction of Protein-Polyelectrolyte Binding Thermodynamics: Adsorption of Heparin-Analog Polysulfates to the SARS-CoV-2 Spike Protein RBD.

Neander L, Hannemann C, Netz R, Sahoo A JACS Au. 2025; 5(1):204-216.

PMID: 39886596 PMC: 11775700. DOI: 10.1021/jacsau.4c00886.

Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic.

Furnon W, Cowton V, De Lorenzo G, Orton R, Herder V, Cantoni D Nat Microbiol. 2025; 10(1):77-93.

PMID: 39753670 PMC: 11726466. DOI: 10.1038/s41564-024-01878-5.

CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.

Hwang W, Austin S, Blondel A, Boittier E, Boresch S, Buck M J Phys Chem B. 2024; 128(41):9976-10042.

PMID: 39303207 PMC: 11492285. DOI: 10.1021/acs.jpcb.4c04100.

References

Ko J, Park H, Seok C . GalaxyTBM: template-based modeling by building a reliable core and refining unreliable local regions. BMC Bioinformatics. 2012; 13:198. PMC: 3462707. DOI: 10.1186/1471-2105-13-198. View

Jo S, Cheng X, Islam S, Huang L, Rui H, Zhu A . CHARMM-GUI PDB manipulator for advanced modeling and simulations of proteins containing nonstandard residues. Adv Protein Chem Struct Biol. 2014; 96:235-65. PMC: 4739825. DOI: 10.1016/bs.apcsb.2014.06.002. View

Hopkins C, Le Grand S, Walker R, Roitberg A . Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning. J Chem Theory Comput. 2015; 11(4):1864-74. DOI: 10.1021/ct5010406. View

Dickson C, Madej B, Skjevik A, Betz R, Teigen K, Gould I . Lipid14: The Amber Lipid Force Field. J Chem Theory Comput. 2014; 10(2):865-879. PMC: 3985482. DOI: 10.1021/ct4010307. View

Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H . Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020; 581(7807):221-224. PMC: 7328981. DOI: 10.1038/s41586-020-2179-y. View

Park S, Lee J, Qi Y, Kern N, Lee H, Jo S . CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates. Glycobiology. 2019; 29(4):320-331. PMC: 6422236. DOI: 10.1093/glycob/cwz003. View

Jo S, Lim J, Klauda J, Im W . CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes. Biophys J. 2009; 97(1):50-8. PMC: 2711372. DOI: 10.1016/j.bpj.2009.04.013. View

Eastman P, Swails J, Chodera J, McGibbon R, Zhao Y, Beauchamp K . OpenMM 7: Rapid development of high performance algorithms for molecular dynamics. PLoS Comput Biol. 2017; 13(7):e1005659. PMC: 5549999. DOI: 10.1371/journal.pcbi.1005659. View

Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q . Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020; 367(6485):1444-1448. PMC: 7164635. DOI: 10.1126/science.abb2762. View

10.

Shajahan A, Supekar N, Gleinich A, Azadi P . Deducing the N- and O-glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2. Glycobiology. 2020; 30(12):981-988. PMC: 7239183. DOI: 10.1093/glycob/cwaa042. View

11.

Croll T . ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps. Acta Crystallogr D Struct Biol. 2018; 74(Pt 6):519-530. PMC: 6096486. DOI: 10.1107/S2059798318002425. View

12.

Best R, Zhu X, Shim J, Lopes P, Mittal J, Feig M . Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles. J Chem Theory Comput. 2013; 8(9):3257-3273. PMC: 3549273. DOI: 10.1021/ct300400x. View

13.

Kong Y, Janssen B, Malinauskas T, Vangoor V, Coles C, Kaufmann R . Structural Basis for Plexin Activation and Regulation. Neuron. 2016; 91(3):548-60. PMC: 4980550. DOI: 10.1016/j.neuron.2016.06.018. View

14.

Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z . Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell. 2020; 181(4):894-904.e9. PMC: 7144619. DOI: 10.1016/j.cell.2020.03.045. View

15.

Grant O, Montgomery D, Ito K, Woods R . Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition. Sci Rep. 2020; 10(1):14991. PMC: 7490396. DOI: 10.1038/s41598-020-71748-7. View

16.

Lee J, Patel D, Stahle J, Park S, Kern N, Kim S . CHARMM-GUI Membrane Builder for Complex Biological Membrane Simulations with Glycolipids and Lipoglycans. J Chem Theory Comput. 2018; 15(1):775-786. DOI: 10.1021/acs.jctc.8b01066. View

17.

Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C, Abiona O . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483):1260-1263. PMC: 7164637. DOI: 10.1126/science.abb2507. View

18.

Soding J . Protein homology detection by HMM-HMM comparison. Bioinformatics. 2004; 21(7):951-60. DOI: 10.1093/bioinformatics/bti125. View

19.

Case D, Cheatham 3rd T, Darden T, Gohlke H, Luo R, Merz Jr K . The Amber biomolecular simulation programs. J Comput Chem. 2005; 26(16):1668-88. PMC: 1989667. DOI: 10.1002/jcc.20290. View

20.

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View