{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T23:13:48Z","timestamp":1773184428506,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011955","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000}}],"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006710","name":"Wayne State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Energy Research Scientific Computing"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The COVID-19 pandemic, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred an urgent need for effective therapeutic interventions. The spike glycoprotein of the SARS-CoV-2 is crucial for infiltrating host cells, rendering it a key candidate for drug development. By interacting with the human angiotensin-converting enzyme 2 (ACE2) receptor, the spike initiates the infection of SARS-CoV-2. Linoleate is known to bind the spike glycoprotein, subsequently reducing its interaction with ACE2. However, the detailed mechanisms underlying the protein-ligand interaction remain unclear. In this study, we characterized the pathways of ligand dissociation and the conformational changes associated with the spike glycoprotein by using ligand Gaussian accelerated molecular dynamics (LiGaMD). Our simulations resulted in eight complete ligand dissociation trajectories, unveiling two distinct ligand unbinding pathways. The preference between these two pathways depends on the gate distance between two \u03b1-helices in the receptor binding domain (RBD) and the position of the N-linked glycan at N343. Our study also highlights the essential contributions of K417, N121 glycan, and N165 glycan in ligand unbinding, which are equally crucial in enhancing spike-ACE2 binding. We suggest that the presence of the ligand influences the motions of these residues and glycans, consequently reducing accessibility for spike-ACE2 binding. These findings enhance our understanding of ligand dissociation from the spike glycoprotein and offer significant implications for drug design strategies in the battle against COVID-19.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011955","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T14:02:52Z","timestamp":1709820172000},"page":"e1011955","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mechanistic insights into ligand dissociation from the SARS-CoV-2 spike glycoprotein"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1524-2489","authenticated-orcid":true,"given":"Timothy","family":"Hasse","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esra","family":"Mantei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rezvan","family":"Shahoei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shristi","family":"Pawnikar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinglong","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3257-6170","authenticated-orcid":true,"given":"Yu-ming M.","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"issue":"10223","key":"pcbi.1011955.ref001","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0140-6736(20)30154-9","article-title":"A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster.","volume":"395","author":"JFW Chan","year":"2020","journal-title":"The Lancet"},{"issue":"10224","key":"pcbi.1011955.ref002","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.","volume":"395","author":"R Lu","year":"2020","journal-title":"The Lancet"},{"issue":"1","key":"pcbi.1011955.ref003","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"CB Jackson","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pcbi.1011955.ref004","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1186\/s13054-020-03120-0","article-title":"Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19.","volume":"24","author":"W Ni","year":"2020","journal-title":"Crit Care"},{"issue":"2","key":"pcbi.1011955.ref005","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1021\/acscentsci.2c01190","article-title":"In silico discovery of small molecule modulators targeting the achilles\u2019 heel of SARS-CoV-2 spike protein.","volume":"9","author":"Q Wang","year":"2023","journal-title":"ACS Cent Sci."},{"issue":"6","key":"pcbi.1011955.ref006","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1021\/acsinfecdis.1c00070","article-title":"Small-molecule inhibitors of the coronavirus spike: ACE2 protein\u2013protein interaction as blockers of viral attachment and entry for SARS-CoV-2.","volume":"7","author":"D Bojadzic","year":"2021","journal-title":"ACS Infect Dis."},{"key":"pcbi.1011955.ref007","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.coviro.2021.08.010","article-title":"Structure of SARS-CoV-2 spike protein.","volume":"50","author":"J Zhang","year":"2021","journal-title":"Current Opinion in Virology."},{"issue":"9","key":"pcbi.1011955.ref008","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19.","volume":"41","author":"Y Huang","year":"2020","journal-title":"Acta Pharmacol Sin."},{"key":"pcbi.1011955.ref009","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"D Wrapp","year":"2020","journal-title":"Science"},{"issue":"7807","key":"pcbi.1011955.ref010","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"J Lan","year":"2020","journal-title":"Nature"},{"issue":"3","key":"pcbi.1011955.ref011","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41594-022-00735-5","article-title":"The SARS-CoV-2 spike reversibly samples an open-trimer conformation exposing novel epitopes","volume":"29","author":"SM Costello","year":"2022","journal-title":"Nat Struct Mol Biol"},{"issue":"7838","key":"pcbi.1011955.ref012","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s41586-020-2665-2","article-title":"Structures and distributions of SARS-CoV-2 spike proteins on intact virions","volume":"588","author":"Z Ke","year":"2020","journal-title":"Nature"},{"issue":"2","key":"pcbi.1011955.ref013","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1080\/17460441.2022.2002298","article-title":"The prediction of protein\u2013ligand unbinding for modern drug discovery.","volume":"17","author":"Q Zhang","year":"2022","journal-title":"Expert Opin Drug Discov."},{"issue":"2","key":"pcbi.1011955.ref014","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jsps.2016.07.002","article-title":"An overview of pharmacodynamic modelling, ligand-binding approach and its application in clinical practice.","volume":"25","author":"MS Salahudeen","year":"2017","journal-title":"Saudi Pharm J.Feb"},{"issue":"3","key":"pcbi.1011955.ref015","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1134\/S199075082003004X","article-title":"Ligand\u2013receptor binding kinetics in drug design.","volume":"14","author":"DV Borisov","year":"2020","journal-title":"Biochem Moscow Suppl Ser B."},{"issue":"10","key":"pcbi.1011955.ref016","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.tibs.2019.04.004","article-title":"Drug\u2013target association kinetics in drug discovery.","volume":"44","author":"AP IJzerman","year":"2019","journal-title":"Trends in Biochem Sci."},{"key":"pcbi.1011955.ref017","doi-asserted-by":"crossref","first-page":"107986","DOI":"10.1016\/j.biotechadv.2022.107986","article-title":"Dias AMGC, Roque ACA. Native, engineered and de novo designed ligands targeting the SARS-CoV-2 spike protein","volume":"59","author":"CFS Costa","year":"2022","journal-title":"Biotechnology Advances"},{"issue":"6","key":"pcbi.1011955.ref018","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1021\/acscentsci.0c01708","article-title":"Discovery of cyclic peptide ligands to the SARS-CoV-2 spike protein using mRNA display.","volume":"7","author":"A Norman","year":"2021","journal-title":"ACS Cent Sci."},{"issue":"2","key":"pcbi.1011955.ref019","doi-asserted-by":"crossref","first-page":"330","DOI":"10.3390\/v14020330","article-title":"Carbohydrate ligands for COVID-19 spike proteins","volume":"14","author":"YK Lee","year":"2022","journal-title":"Viruses"},{"issue":"1","key":"pcbi.1011955.ref020","doi-asserted-by":"crossref","first-page":"5207","DOI":"10.1038\/s41598-021-84850-1","article-title":"Polyunsaturated \u03c9-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry.","volume":"11","author":"A Goc","year":"2021","journal-title":"Sci Rep."},{"key":"pcbi.1011955.ref021","doi-asserted-by":"crossref","first-page":"668330","DOI":"10.3389\/fphys.2021.668330","article-title":"Long chain fatty acids as modulators of immune cells function: Contribution of FFA1 and FFA4 receptors.","volume":"12","author":"MA Hidalgo","year":"2021","journal-title":"Front Physiol."},{"key":"pcbi.1011955.ref022","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bcp.2016.03.017","article-title":"Metabolism meets immunity: The role of free fatty acid receptors in the immune system","volume":"114","author":"E Alvarez-Curto","year":"2016","journal-title":"Biochem Pharmacol"},{"issue":"6517","key":"pcbi.1011955.ref023","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1126\/science.abd3255","article-title":"Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein","volume":"370","author":"C Toelzer","year":"2020","journal-title":"Science"},{"issue":"47","key":"pcbi.1011955.ref024","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adc9179","article-title":"The free fatty acid\u2013binding pocket is a conserved hallmark in pathogenic \u03b2-coronavirus spike proteins from SARS-CoV to Omicron","volume":"8","author":"C Toelzer","year":"2022","journal-title":"Sci Adv"},{"issue":"10","key":"pcbi.1011955.ref025","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/acscentsci.0c01056","article-title":"Beyond shielding: The roles of glycans in the SARS-CoV-2 spike protein.","volume":"6","author":"L Casalino","year":"2020","journal-title":"ACS Cent Sci."},{"issue":"28","key":"pcbi.1011955.ref026","doi-asserted-by":"crossref","first-page":"e2119761119","DOI":"10.1073\/pnas.2119761119","article-title":"Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors","volume":"119","author":"K Kapoor","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"pcbi.1011955.ref027","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.3390\/ijms24044192","article-title":"Identifying SARS-CoV-2 drugs binding to the spike fatty acid binding pocket using in silico docking and molecular dynamics.","volume":"24","author":"S Piplani","year":"2023","journal-title":"Int J Mol Sci."},{"issue":"13","key":"pcbi.1011955.ref028","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1002\/anie.202015639","article-title":"Molecular simulations suggest vitamins, retinoids and steroids as ligands of the free fatty acid pocket of the SARS-CoV-2 spike protein","volume":"60","author":"DK Shoemark","year":"2021","journal-title":"Angew Chem Int Ed"},{"key":"pcbi.1011955.ref029","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.csbj.2021.12.011","article-title":"The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour","volume":"20","author":"ASF Oliveira","year":"2022","journal-title":"Comput Struct Biotechnol J"},{"issue":"9","key":"pcbi.1011955.ref030","doi-asserted-by":"crossref","first-page":"5526","DOI":"10.1021\/acs.jctc.0c00395","article-title":"Ligand gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics.","volume":"16","author":"Y Miao","year":"2020","journal-title":"J Chem Theory Comput."},{"issue":"18","key":"pcbi.1011955.ref031","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1016\/j.bpj.2021.08.026","article-title":"Multiscale computational study of ligand binding pathways: Case of p38 MAP kinase and its inhibitors","volume":"120","author":"M. Huang Y ming","year":"2021","journal-title":"Biophysical Journal"},{"key":"pcbi.1011955.ref032","doi-asserted-by":"crossref","first-page":"W522","DOI":"10.1093\/nar\/gkm276","article-title":"PDB2PQR: Expanding and upgrading automated preparation of biomolecular structures for molecular simulations","volume":"35","author":"TJ Dolinsky","year":"2007","journal-title":"Nucleic Acids Research"},{"issue":"4","key":"pcbi.1011955.ref033","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/glycob\/cwz003","article-title":"CHARMM-GUI glycan modeler for modeling and simulation of carbohydrates and glycoconjugates.","volume":"29","author":"SJ Park","year":"2019","journal-title":"Glycobiol."},{"issue":"19","key":"pcbi.1011955.ref034","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1093\/bioinformatics\/btx358","article-title":"Glycan Reader is improved to recognize most sugar types and chemical modifications in the Protein Data Bank.","volume":"33","author":"SJ Park","year":"2017","journal-title":"Bioinform.Oct"},{"issue":"2","key":"pcbi.1011955.ref035","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/wcms.1121","article-title":"An overview of the AMBER biomolecular simulation package: AMBER biomolecular simulation package.","volume":"3","author":"R Salomon-Ferrer","year":"2013","journal-title":"WIREs Comput Mol Sci."},{"issue":"1","key":"pcbi.1011955.ref036","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1021\/acs.jctc.9b00591","article-title":"ff19SB: Amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution.","volume":"16","author":"C Tian","year":"2020","journal-title":"J Chem Theory Comput.Jan"},{"issue":"4","key":"pcbi.1011955.ref037","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/jcc.20820","article-title":"GLYCAM06: A generalizable biomolecular force field","volume":"29","author":"KN Kirschner","year":"2008","journal-title":"J Comput Chem"},{"issue":"11","key":"pcbi.1011955.ref038","doi-asserted-by":"crossref","first-page":"114502","DOI":"10.1063\/5.0019056","article-title":"A fast and high-quality charge model for the next generation general AMBER force field","volume":"153","author":"X He","year":"2020","journal-title":"J Chem Phys"},{"issue":"18","key":"pcbi.1011955.ref039","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1021\/jp973084f","article-title":"All-atom empirical potential for molecular modeling and dynamics studies of proteins","volume":"102","author":"AD MacKerell","year":"1998","journal-title":"J Phys Chem B"},{"issue":"2","key":"pcbi.1011955.ref040","doi-asserted-by":"crossref","first-page":"024103","DOI":"10.1063\/1.4954990","article-title":"A simple and accurate algorithm for path integral molecular dynamics with the langevin thermostat","volume":"145","author":"J Liu","year":"2016","journal-title":"J Chem Phys"},{"issue":"19","key":"pcbi.1011955.ref041","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh ewald method","volume":"103","author":"U Essmann","year":"1995","journal-title":"J Chem Phys"},{"issue":"3","key":"pcbi.1011955.ref042","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"JP Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"issue":"1","key":"pcbi.1011955.ref043","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"W Humphrey","year":"1996","journal-title":"J Mol Graph"},{"issue":"7","key":"pcbi.1011955.ref044","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data.","volume":"9","author":"DR Roe","year":"2013","journal-title":"J Chem Theory Comput."},{"issue":"7","key":"pcbi.1011955.ref045","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1021\/ct500090q","article-title":"Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation.","volume":"10","author":"Y Miao","year":"2014","journal-title":"J Chem Theory Comput."},{"issue":"6501","key":"pcbi.1011955.ref046","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1126\/science.abb9983","article-title":"Site-specific glycan analysis of the SARS-CoV-2 spike","volume":"369","author":"Y Watanabe","year":"2020","journal-title":"Science"},{"issue":"2","key":"pcbi.1011955.ref047","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein.","volume":"181","author":"AC Walls","year":"2020","journal-title":"Cell."},{"issue":"6","key":"pcbi.1011955.ref048","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.neuron.2018.08.011","article-title":"Molecular dynamics simulation for all","volume":"99","author":"SA Hollingsworth","year":"2018","journal-title":"Neuron"},{"issue":"2","key":"pcbi.1011955.ref049","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.sbi.2009.03.004","article-title":"Long-timescale molecular dynamics simulations of protein structure and function","volume":"19","author":"JL Klepeis","year":"2009","journal-title":"Curr Opin Struct Biol"},{"issue":"5","key":"pcbi.1011955.ref050","doi-asserted-by":"crossref","first-page":"E386","DOI":"10.1073\/pnas.1424461112","article-title":"Kinetics of protein\u2013ligand unbinding: Predicting pathways, rates, and rate-limiting steps","volume":"112","author":"P Tiwary","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"pcbi.1011955.ref051","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/wcms.66","article-title":"Umbrella sampling.","volume":"1","author":"J. K\u00e4stner","year":"2011","journal-title":"WIREs Comput Mol Sci.Nov"},{"issue":"2","key":"pcbi.1011955.ref052","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0021-9991(77)90121-8","article-title":"Nonphysical Sampling Distributions in Monte Carlo Free-Energy Estimation: Umbrella Sampling","volume":"23","author":"GM Torrie","year":"1997","journal-title":"J Comput Phys"},{"issue":"4","key":"pcbi.1011955.ref053","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s42254-020-0153-0","article-title":"Exploring complex free-energy landscapes by metadynamics.","volume":"2","author":"G Bussi","year":"2020","journal-title":"Nat Rev Phys."},{"issue":"12","key":"pcbi.1011955.ref054","doi-asserted-by":"crossref","first-page":"126601","DOI":"10.1088\/0034-4885\/71\/12\/126601","article-title":"Metadynamics: a method to simulate rare events and reconstruct the free energy in biophysics, chemistry and material science","volume":"71","author":"A Laio","year":"2008","journal-title":"Rep Prog Phys"},{"issue":"3","key":"pcbi.1011955.ref055","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1021\/jp506633n","article-title":"The adaptive biasing force method: everything you always wanted to know but were afraid to ask","volume":"119","author":"J Comer","year":"2015","journal-title":"J Phys Chem B"},{"issue":"8","key":"pcbi.1011955.ref056","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1021\/acs.jcim.8b00261","article-title":"Steered molecular dynamics simulation in rational drug design.","volume":"58","author":"PC Do","year":"2018","journal-title":"J Chem Inf Model."},{"issue":"30","key":"pcbi.1011955.ref057","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.1021\/bi3006913","article-title":"Conformational selection or induced fit? A critical appraisal of the kinetic mechanism.","volume":"51","author":"AD Vogt","year":"2012","journal-title":"Biochem."},{"issue":"4","key":"pcbi.1011955.ref058","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.cell.2022.01.001","article-title":"Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2","volume":"185","author":"P Han","year":"2022","journal-title":"Cell"},{"issue":"3","key":"pcbi.1011955.ref059","article-title":"SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid. Fu H, editor","volume":"15","author":"ASF Oliveira","year":"2023","journal-title":"J Mol Cell Biol"},{"issue":"1","key":"pcbi.1011955.ref060","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41392-021-00809-8","article-title":"The glycosylation in SARS-CoV-2 and its receptor ACE2.","volume":"6","author":"Y Gong","year":"2021","journal-title":"Sig Transduct Target Ther."},{"issue":"10","key":"pcbi.1011955.ref061","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41557-021-00758-3","article-title":"A glycan gate controls opening of the SARS-CoV-2 spike protein.","volume":"13","author":"T Sztain","year":"2021","journal-title":"Nat Chem."},{"issue":"2","key":"pcbi.1011955.ref062","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1093\/bib\/bbaa233","article-title":"Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity","volume":"22","author":"S Teng","year":"2021","journal-title":"Brief Bioinform"},{"issue":"1","key":"pcbi.1011955.ref063","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41392-020-00302-8","article-title":"Profiling and characterization of SARS-CoV-2 mutants\u2019 infectivity and antigenicity.","volume":"5","author":"L Wang","year":"2020","journal-title":"Sig Transduct Target Ther."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011955","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011955","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T13:45:10Z","timestamp":1711115110000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011955"}},"subtitle":[],"editor":[{"given":"Alexander","family":"MacKerell","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011955","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.29.569184","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,7]]}}}