{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:01:48Z","timestamp":1777521708480,"version":"3.51.4"},"reference-count":79,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T00:00:00Z","timestamp":1724544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Food and Agriculture","award":["ILLU-802-909"],"award-info":[{"award-number":["ILLU-802-909"]}]},{"name":"National Institute of Food and Agriculture","award":["ILLU-483-625"],"award-info":[{"award-number":["ILLU-483-625"]}]},{"name":"Office of Research and Office of International Programs, College of Agricultural, Consumer and Environmental Sciences of the University of Illinois at Urbana-Champaign","award":["ILLU-802-909"],"award-info":[{"award-number":["ILLU-802-909"]}]},{"name":"Office of Research and Office of International Programs, College of Agricultural, Consumer and Environmental Sciences of the University of Illinois at Urbana-Champaign","award":["ILLU-483-625"],"award-info":[{"award-number":["ILLU-483-625"]}]},{"name":"New Frontiers Initiative of the National Center for Supercomputing Applications (NCSA)","award":["ILLU-802-909"],"award-info":[{"award-number":["ILLU-802-909"]}]},{"name":"New Frontiers Initiative of the National Center for Supercomputing Applications (NCSA)","award":["ILLU-483-625"],"award-info":[{"award-number":["ILLU-483-625"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The COVID-19 pandemic saw the emergence of various Variants of Concern (VOCs) that took the world by storm, often replacing the ones that preceded them. The characteristic mutant constellations of these VOCs increased viral transmissibility and infectivity. Their origin and evolution remain puzzling. With the help of data mining efforts and the GISAID database, a chronology of 22 haplotypes described viral evolution up until 23 July 2023. Since the three-dimensional atomic structures of proteins corresponding to the identified haplotypes are not available, ab initio methods were here utilized. Regions of intrinsic disorder proved to be important for viral evolution, as evidenced by the targeted change to the nucleocapsid (N) protein at the sequence, structure, and biochemical levels. The linker region of the N-protein, which binds to the RNA genome and self-oligomerizes for efficient genome packaging, was greatly impacted by mutations throughout the pandemic, followed by changes in structure and intrinsic disorder. Remarkably, VOC constellations acted co-operatively to balance the more extreme effects of individual haplotypes. Our strategy of mapping the dynamic evolutionary landscape of genetically linked mutations to the N-protein structure demonstrates the utility of ab initio modeling and deep learning tools for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/v16091358","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T01:48:49Z","timestamp":1724636929000},"page":"1358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Nucleocapsid Protein Variants"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-2460","authenticated-orcid":false,"given":"Muhammad Asif","family":"Ali","sequence":"first","affiliation":[{"name":"Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-4121","authenticated-orcid":false,"given":"Gustavo","family":"Caetano-Anoll\u00e9s","sequence":"additional","affiliation":[{"name":"Evolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,25]]},"reference":[{"key":"ref_1","unstructured":"WHO (2024, July 01). COVID-19 Dashboard, COVID-19 Deaths. Available online: https:\/\/data.who.int\/dashboards\/covid19\/cases."},{"key":"ref_2","unstructured":"StatsAmerica (2024, July 01). States in Profile, Population Estimate for 2023, Ranked List. Available online: https:\/\/www.statsamerica.org\/sip\/rank_list.aspx?rank_label=pop1&ct=S18."},{"key":"ref_3","unstructured":"United Nations, Department of Economic and Social Affairs, Population Division (2024, July 01). World Population Prospects. Available online: https:\/\/population.un.org\/wpp\/Download\/Standard\/Population\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.18683\/germs.2019.1155","article-title":"Middle East Respiratory Syndrome Coronavirus (MERS-CoV): A Review","volume":"9","author":"Ramadan","year":"2019","journal-title":"Germs"},{"key":"ref_5","unstructured":"Hodgens, A., and Gupta, V. (2022). Severe Acute Respiratory Syndrome. StatPearls, StatPearls Publishing."},{"key":"ref_6","unstructured":"(2024, July 01). Summary of Probable SARS Cases with Onset of Illness from 1 November 2002 to 31 July 2003. Available online: https:\/\/www.who.int\/publications\/m\/item\/summary-of-probable-sars-cases-with-onset-of-illness-from-1-november-2002-to-31-july-2003."},{"key":"ref_7","unstructured":"(2024, July 01). MERS-CoV Worldwide Overview. Available online: https:\/\/www.ecdc.europa.eu\/en\/middle-east-respiratory-syndrome-coronavirus-mers-cov-situation-update."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2112","DOI":"10.1002\/rmv.2112","article-title":"Comparison of Confirmed COVID-19 with SARS and MERS Cases-Clinical Characteristics, Laboratory Findings, Radiographic Signs and Outcomes: A Systematic Review and Meta-analysis","volume":"30","author":"Pormohammad","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4103\/jfmpc.jfmpc_839_21","article-title":"SARS, MERS and CoVID-19: An Overview and Comparison of Clinical, Laboratory and Radiological Features","volume":"11","author":"Pustake","year":"2022","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1056\/NEJMc2001737","article-title":"SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients","volume":"382","author":"Zou","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2000180","DOI":"10.2807\/1560-7917.ES.2020.25.10.2000180","article-title":"Estimating the Asymptomatic Proportion of Coronavirus Disease 2019 (COVID-19) Cases on Board the Diamond Princess Cruise Ship, Yokohama, Japan, 2020","volume":"25","author":"Mizumoto","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113928","DOI":"10.1016\/j.socscimed.2021.113928","article-title":"COVID-19 Information on Social Media and Preventive Behaviors: Managing the Pandemic through Personal Responsibility","volume":"277","author":"Liu","year":"2021","journal-title":"Soc. Sci. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A Pneumonia Outbreak Associated with a New Coronavirus of Probable Bat Origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tomaszewski, T., Ali, M.A., Caetano-Anoll\u00e9s, K., and Caetano-Anoll\u00e9s, G. (2023). Seasonal Effects Decouple SARS-CoV-2 Haplotypes Worldwide. F1000Research, 12.","DOI":"10.12688\/f1000research.131522.1"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ali, M.A., and Caetano-Anoll\u00e9s, G. (2024). AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Spike Protein Variants. Biology, 13.","DOI":"10.20944\/preprints202407.0591.v1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12985-023-01968-6","article-title":"The SARS-CoV-2 Nucleocapsid Protein: Its Role in the Viral Life Cycle, Structure and Functions, and Use as a Potential Target in the Development of Vaccines and Diagnostics","volume":"20","author":"Wu","year":"2023","journal-title":"Virol. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tomaszewski, T., DeVries, R.S., Dong, M., Bhatia, G., Norsworthy, M.D., Zheng, X., and Caetano-Anoll\u00e9s, G. (2020). New Pathways of Mutational Change in SARS-CoV-2 Proteomes Involve Regions of Intrinsic Disorder Important for Virus Replication and Release. Evol. Bioinform. Online, 16.","DOI":"10.1177\/1176934320965149"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e105938","DOI":"10.15252\/embj.2020105938","article-title":"Structures of the SARS-CoV-2 Nucleocapsid and Their Perspectives for Drug Design","volume":"39","author":"Peng","year":"2020","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1002\/pro.3909","article-title":"Architecture and Self-assembly of the SARS-CoV-2 Nucleocapsid Protein","volume":"29","author":"Ye","year":"2020","journal-title":"Protein Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1128\/JVI.02001-08","article-title":"Multiple Nucleic Acid Binding Sites and Intrinsic Disorder of Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Implications for Ribonucleocapsid Protein Packaging","volume":"83","author":"Chang","year":"2009","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8311","DOI":"10.1073\/pnas.0700329104","article-title":"Intrinsic Disorder as a Mechanism to Optimize Allosteric Coupling in Proteins","volume":"104","author":"Hilser","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.antiviral.2013.12.009","article-title":"The SARS Coronavirus Nucleocapsid Protein\u2014Forms and Functions","volume":"103","author":"Chang","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41467-020-20768-y","article-title":"The SARS-CoV-2 Nucleocapsid Phosphoprotein Forms Mutually Exclusive Condensates with RNA and the Membrane-Associated M Protein","volume":"12","author":"Lu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Oh, S.J., and Shin, O.S. (2021). SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response. Cells, 10.","DOI":"10.3390\/cells10030530"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0065-3527(05)64006-7","article-title":"Molecular Interactions in the Assembly of Coronaviruses","volume":"64","author":"Rottier","year":"2005","journal-title":"Adv. Virus Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1038\/s41467-020-19619-7","article-title":"SARS-CoV-2 Structure and Replication Characterized by in Situ Cryo-Electron Tomography","volume":"11","author":"Klein","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.virol.2006.11.027","article-title":"The Intracellular Sites of Early Replication and Budding of SARS-Coronavirus","volume":"361","author":"Stertz","year":"2007","journal-title":"Virology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/jama.2020.27124","article-title":"Genetic Variants of SARS-CoV-2\u2014What Do They Mean?","volume":"325","author":"Lauring","year":"2021","journal-title":"JAMA"},{"key":"ref_29","unstructured":"Singh, D.B., and Pathak, R.K. (2022). Chapter 11\u2014Protein Structure Prediction. Bioinformatics, Academic Press."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/cfg.305","article-title":"Ab Initio Protein Structure Prediction Using Pathway Models","volume":"4","author":"Yuan","year":"2003","journal-title":"Comp. Funct. Genom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1002\/prot.26237","article-title":"Critical Assessment of Methods of Protein Structure Prediction (CASP)\u2014Round XIV","volume":"89","author":"Kryshtafovych","year":"2021","journal-title":"Proteins: Struct. Funct. Bioinform."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/prot.26617","article-title":"Critical Assessment of Methods of Protein Structure Prediction (CASP)\u2014Round XV","volume":"91","author":"Kryshtafovych","year":"2023","journal-title":"Proteins: Struct. Funct. Bioinform."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ford, C.T., Jacob Machado, D., and Janies, D.A. (2022). Predictions of the SARS-CoV-2 Omicron Variant (B.1.1.529) Spike Protein Receptor-Binding Domain Structure and Neutralizing Antibody Interactions. Front. Virol., 2.","DOI":"10.3389\/fviro.2022.830202"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41597-023-02035-z","article-title":"SARS-CoV-2 Receptor-Binding Domain Deep Mutational AlphaFold2 Structures","volume":"10","author":"Kilim","year":"2023","journal-title":"Sci. Data"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9781758","DOI":"10.34133\/2022\/9781758","article-title":"Structural Comparison and Drug Screening of Spike Proteins of Ten SARS-CoV-2 Variants","volume":"2022","author":"Yang","year":"2022","journal-title":"Research"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/bs.mim.2022.03.003","article-title":"Chapter 8\u2014The Emergence of SARS-CoV-2 Variants of Concern in Australia by Haplotype Coalescence Reveals a Continental Link to COVID-19 Seasonality","volume":"Volume 50","author":"Pavia","year":"2022","journal-title":"Methods in Microbiology"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Burra, P., Soto-D\u00edaz, K., Chalen, I., Gonzalez-Ricon, R.J., Istanto, D., and Caetano-Anoll\u00e9s, G. (2021). Temperature and Latitude Correlate with SARS-CoV-2 Epidemiological Variables but Not with Genomic Change Worldwide. Evol. Bioinform. Online, 17.","DOI":"10.1177\/1176934321989695"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hernandez, N., and Caetano-Anoll\u00e9s, G. (2023). Worldwide Correlations Support COVID-19 Seasonal Behavior and Impact of Global Change. Evol. Bioinform., 19.","DOI":"10.1177\/11769343231169377"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Muradyan, N., Arakelov, V., Sargsyan, A., Paronyan, A., Arakelov, G., and Nazaryan, K. (2024). Impact of Mutations on the Stability of SARS-CoV-2 Nucleocapsid Protein Structure. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-55157-8"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"pgac049","DOI":"10.1093\/pnasnexus\/pgac049","article-title":"Plasticity in Structure and Assembly of SARS-CoV-2 Nucleocapsid Protein","volume":"1","author":"Zhao","year":"2022","journal-title":"PNAS Nexus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1002\/jmv.26626","article-title":"Evolutionary Dynamics of SARS-CoV-2 Nucleocapsid Protein and Its Consequences","volume":"93","author":"Rahman","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making Protein Folding Accessible to All","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1093\/bioinformatics\/btt473","article-title":"lDDT: A Local Superposition-Free Score for Comparing Protein Structures and Models Using Distance Difference Tests","volume":"29","author":"Mariani","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/prot.20264","article-title":"Scoring Function for Automated Assessment of Protein Structure Template Quality","volume":"57","author":"Zhang","year":"2004","journal-title":"Proteins"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/s41592-022-01585-1","article-title":"US-Align: Universal Structure Alignments of Proteins, Nucleic Acids, and Macromolecular Complexes","volume":"19","author":"Zhang","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1093\/bioinformatics\/btl461","article-title":"Bio3d: An R Package for the Comparative Analysis of Protein Structures","volume":"22","author":"Grant","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_49","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Core Team."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D Graphics Environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array Programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"ref_52","unstructured":"The pandas development team Pandas v.2.2.2 2024."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.1093\/nar\/gkg571","article-title":"LGA: A Method for Finding 3D Similarities in Protein Structures","volume":"31","author":"Zemla","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"W111","DOI":"10.1093\/nar\/gki457","article-title":"AS2TS System for Protein Structure Modeling and Analysis","volume":"33","author":"Zemla","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_55","unstructured":"LGA (2024, July 02). Protein Structure Comparison Facility. Available online: http:\/\/proteinmodel.org\/AS2TS\/LGA\/lga.html."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/j.1460-2075.1986.tb04288.x","article-title":"The Relation between the Divergence of Sequence and Structure in Proteins","volume":"5","author":"Chothia","year":"1986","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1359-0278(98)00019-4","article-title":"What Is the Probability of a Chance Prediction of a Protein Structure with an Rmsd of 6 \u00e5?","volume":"3","author":"Reva","year":"1998","journal-title":"Fold. Des."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13073-021-00910-1","article-title":"Landscape and Selection of Vaccine Epitopes in SARS-CoV-2","volume":"13","author":"Smith","year":"2021","journal-title":"Genome Med."},{"key":"ref_59","unstructured":"(2024, July 01). TM-Score: Quantitative Assessment of Similarity between Protein Structures. Available online: https:\/\/zhanggroup.org\/TM-score\/."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/s41594-022-00849-w","article-title":"A Structural Biology Community Assessment of AlphaFold2 Applications","volume":"29","author":"Akdel","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Bruley, A., Mornon, J.-P., Duprat, E., and Callebaut, I. (2022). Digging into the 3D Structure Predictions of AlphaFold2 with Low Confidence: Disorder and Beyond. Biomolecules, 12.","DOI":"10.3390\/biom12101467"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wilson, C.J., Choy, W.-Y., and Karttunen, M. (2022). AlphaFold2: A Role for Disordered Protein\/Region Prediction?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094591"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2304302120","DOI":"10.1073\/pnas.2304302120","article-title":"Systematic Identification of Conditionally Folded Intrinsically Disordered Regions by AlphaFold2","volume":"120","author":"Alderson","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"W329","DOI":"10.1093\/nar\/gky384","article-title":"IUPred2A: Context-Dependent Prediction of Protein Disorder as a Function of Redox State and Protein Binding","volume":"46","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0959-440X(94)90321-2","article-title":"Normal Mode Analysis of Protein Dynamics","volume":"4","author":"Case","year":"1994","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bauer, J.A., Pavlovi\u0107, J., and Bauerov\u00e1-Hlinkov\u00e1, V. (2019). Normal Mode Analysis as a Routine Part of a Structural Investigation. Molecules, 24.","DOI":"10.3390\/molecules24183293"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/pro.3923","article-title":"The Bio3D Packages for Structural Bioinformatics","volume":"30","author":"Grant","year":"2021","journal-title":"Protein Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s12551-017-0330-2","article-title":"Normal Mode Analysis as a Method to Derive Protein Dynamics Information from the Protein Data Bank","volume":"9","author":"Wako","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Dinesh, D.C., Chalupska, D., Silhan, J., Koutna, E., Nencka, R., Veverka, V., and Boura, E. (2020). Structural Basis of RNA Recognition by the SARS-CoV-2 Nucleocapsid Phosphoprotein. PLoS Pathog., 16.","DOI":"10.1101\/2020.04.02.022194"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1110\/ps.04882105","article-title":"Normal Modes for Predicting Protein Motions: A Comprehensive Database Assessment and Associated Web Tool","volume":"14","author":"Alexandrov","year":"2005","journal-title":"Protein Sci. A Publ. Protein Soc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1038\/s41467-021-21953-3","article-title":"The SARS-CoV-2 Nucleocapsid Protein Is Dynamic, Disordered, and Phase Separates with RNA","volume":"12","author":"Cubuk","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_73","unstructured":"RCSB Protein Data Bank (2024, July 02). RCSB PDB: Homepage. Available online: https:\/\/www.rcsb.org\/."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bai, Z., Cao, Y., Liu, W., and Li, J. (2021). The SARS-CoV-2 Nucleocapsid Protein and Its Role in Viral Structure, Biological Functions, and a Potential Target for Drug or Vaccine Mitigation. Viruses, 13.","DOI":"10.3390\/v13061115"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1111\/j.1742-4658.2008.06564.x","article-title":"Phosphorylation of the Arginine\/Serine Dipeptide-Rich Motif of the Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein Modulates Its Multimerization, Translation Inhibitory Activity and Cellular Localization","volume":"275","author":"Peng","year":"2008","journal-title":"FEBS J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jmb.2007.11.093","article-title":"Solution Structure of the C-Terminal Dimerization Domain of SARS Coronavirus Nucleocapsid Protein Solved by the SAIL-NMR Method","volume":"380","author":"Takeda","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.jmb.2007.02.069","article-title":"Structure of the SARS Coronavirus Nucleocapsid Protein RNA-Binding Dimerization Domain Suggests a Mechanism for Helical Packaging of Viral RNA","volume":"368","author":"Chen","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Chang, C., Chen, C.-M.M., Chiang, M., Hsu, Y., and Huang, T. (2013). Transient Oligomerization of the SARS-CoV N Protein--Implication for Virus Ribonucleoprotein Packaging. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065045"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11476","DOI":"10.1128\/JVI.79.17.11476-11486.2005","article-title":"The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein Is Phosphorylated and Localizes in the Cytoplasm by 14-3-3-Mediated Translocation","volume":"79","author":"Surjit","year":"2005","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/9\/1358\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:32Z","timestamp":1760110952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/9\/1358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,25]]},"references-count":79,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["v16091358"],"URL":"https:\/\/doi.org\/10.3390\/v16091358","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,25]]}}}