{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:12:47Z","timestamp":1778220767113,"version":"3.51.4"},"reference-count":93,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100011958","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["8022-00041B"],"award-info":[{"award-number":["8022-00041B"]}],"id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011958","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["8022-00041B"],"award-info":[{"award-number":["8022-00041B"]}],"id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Biochem"],"published-print":{"date-parts":[[2023,6]]},"DOI":"10.1007\/s11010-022-04588-w","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T14:07:46Z","timestamp":1666879666000},"page":"1269-1280","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Stability and expression of SARS-CoV-2 spike-protein mutations"],"prefix":"10.1007","volume":"478","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-3962","authenticated-orcid":false,"given":"Kristoffer T.","family":"B\u00e6k","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-1514","authenticated-orcid":false,"given":"Rukmankesh","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6754-7348","authenticated-orcid":false,"given":"Kasper P.","family":"Kepp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"4588_CR1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","volume":"579","author":"F Wu","year":"2020","unstructured":"Wu F, Zhao S, Yu B et al (2020) A new coronavirus associated with human respiratory disease in China. Nature 579:265\u2013269","journal-title":"Nature"},{"key":"4588_CR2","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","volume":"382","author":"N Zhu","year":"2020","unstructured":"Zhu N, Zhang D, Wang W et al (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382:727\u2013733","journal-title":"N Engl J Med"},{"key":"4588_CR3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3862","author":"M Cevik","year":"2020","unstructured":"Cevik M, Kuppalli K, Kindrachuk J, Peiris M (2020) Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ. https:\/\/doi.org\/10.1136\/bmj.m3862","journal-title":"BMJ"},{"key":"4588_CR4","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1016\/j.cell.2021.02.032","volume":"184","author":"W Dejnirattisai","year":"2021","unstructured":"Dejnirattisai W, Zhou D, Ginn HM et al (2021) The antigenic anatomy of SARS-CoV-2 receptor binding domain. Cell 184:2183-2200.e22. https:\/\/doi.org\/10.1016\/j.cell.2021.02.032","journal-title":"Cell"},{"key":"4588_CR5","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/s41586-021-03291-y","volume":"592","author":"SA Kemp","year":"2021","unstructured":"Kemp SA, Collier DA, Datir RP et al (2021) SARS-CoV-2 evolution during treatment of chronic infection. Nature 592:277\u2013282. https:\/\/doi.org\/10.1038\/s41586-021-03291-y","journal-title":"Nature"},{"key":"4588_CR6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.coviro.2021.07.002","volume":"50","author":"L van Dorp","year":"2021","unstructured":"van Dorp L, Houldcroft CJ, Richard D, Balloux F (2021) COVID-19, the first pandemic in the post-genomic era. Curr Opin Virol 50:40\u201348","journal-title":"Curr Opin Virol"},{"key":"4588_CR7","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","volume":"19","author":"WT Harvey","year":"2021","unstructured":"Harvey WT, Carabelli AM, Jackson B et al (2021) SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol 19:409\u2013424","journal-title":"Nat Rev Microbiol"},{"key":"4588_CR8","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1002\/prot.26042","volume":"89","author":"L Guruprasad","year":"2021","unstructured":"Guruprasad L (2021) Human SARS CoV-2 spike protein mutations. Proteins Struct Funct Bioinforma 89:569\u2013576. https:\/\/doi.org\/10.1002\/prot.26042","journal-title":"Proteins Struct Funct Bioinforma"},{"key":"4588_CR9","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/s41564-020-0688-y","volume":"5","author":"M Letko","year":"2020","unstructured":"Letko M, Marzi A, Munster V (2020) Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 5:562\u2013569","journal-title":"Nat Microbiol"},{"key":"4588_CR10","first-page":"1","volume-title":"Coronaviruses Methods Protoc","author":"AR Fehr","year":"2015","unstructured":"Fehr AR, Perlman S (2015) Coronaviruses: an overview of their replication and pathogenesis. Coronaviruses Methods Protoc. Springer, New York, pp 1\u201323"},{"key":"4588_CR11","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.cell.2020.03.045","volume":"181","author":"Q Wang","year":"2020","unstructured":"Wang Q, Zhang Y, Wu L et al (2020) Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 181:894\u2013904","journal-title":"Cell"},{"issue":"3","key":"4588_CR12","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1021\/acscentsci.0c00272","volume":"6","author":"C Liu","year":"2020","unstructured":"Liu C, Zhou Q, Li Y et al (2020) Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent Sci 6(3):315\u2013331","journal-title":"ACS Cent Sci"},{"key":"4588_CR13","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/s41418-020-00720-9","volume":"28","author":"G Forni","year":"2021","unstructured":"Forni G, Mantovani A (2021) COVID-19 vaccines: where we stand and challenges ahead. Cell Death Differ 28:626\u2013639","journal-title":"Cell Death Differ"},{"key":"4588_CR14","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1126\/science.abh1139","volume":"373","author":"M Yuan","year":"2021","unstructured":"Yuan M, Huang D, Lee C-CD et al (2021) Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants. Science 373:818\u2013823. https:\/\/doi.org\/10.1126\/science.abh1139","journal-title":"Science"},{"key":"4588_CR15","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/s41586-021-04388-0","volume":"602","author":"L Liu","year":"2022","unstructured":"Liu L, Iketani S, Guo Y et al (2022) Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature 602:676\u2013681","journal-title":"Nature"},{"key":"4588_CR16","doi-asserted-by":"publisher","first-page":"e1002929","DOI":"10.1371\/journal.pcbi.1002929","volume":"9","author":"P Dasmeh","year":"2013","unstructured":"Dasmeh P, Serohijos AWR, Kepp KP, Shakhnovich EI (2013) Positively selected sites in cetacean myoglobins contribute to protein stability. PLoS Comput Biol 9:e1002929","journal-title":"PLoS Comput Biol"},{"key":"4588_CR17","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1002\/pro.2071","volume":"21","author":"DA Liberles","year":"2012","unstructured":"Liberles DA, Teichmann SA, Bahar I et al (2012) The interface of protein structure, protein biophysics, and molecular evolution. Protein Sci 21:769\u2013785. https:\/\/doi.org\/10.1002\/pro.2071","journal-title":"Protein Sci"},{"key":"4588_CR18","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.bb.13.060184.002321","volume":"13","author":"M Bajaj","year":"1984","unstructured":"Bajaj M, Blundell T (1984) Evolution and the tertiary structure of proteins. Annu Rev Biophys Bioeng 13:453\u2013492","journal-title":"Annu Rev Biophys Bioeng"},{"key":"4588_CR19","doi-asserted-by":"publisher","first-page":"9916","DOI":"10.1073\/pnas.1017572108","volume":"108","author":"CS Wylie","year":"2011","unstructured":"Wylie CS, Shakhnovich EI (2011) A biophysical protein folding model accounts for most mutational fitness effects in viruses. Proc Natl Acad Sci U S A 108:9916\u20139921. https:\/\/doi.org\/10.1073\/pnas.1017572108","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4588_CR20","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.cell.2008.05.042","volume":"134","author":"DA Drummond","year":"2008","unstructured":"Drummond DA, Wilke CO (2008) Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution. Cell 134:341\u2013352. https:\/\/doi.org\/10.1016\/j.cell.2008.05.042","journal-title":"Cell"},{"key":"4588_CR21","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/protein\/10.1.7","volume":"10","author":"CM Topham","year":"1997","unstructured":"Topham CM, Srinivasan N, Blundell TL (1997) Prediction of the stability of protein mutants based on structural environment-dependent amino acid substitution and propensity tables. Protein Eng 10:7\u201321","journal-title":"Protein Eng"},{"key":"4588_CR22","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/nrm2762","volume":"10","author":"CL Worth","year":"2009","unstructured":"Worth CL, Gong S, Blundell TL (2009) Structural and functional constraints in the evolution of protein families. Nat Rev Mol Cell Biol 10:709","journal-title":"Nat Rev Mol Cell Biol"},{"key":"4588_CR23","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.pbiomolbio.2021.01.003","volume":"160","author":"TL Blundell","year":"2021","unstructured":"Blundell TL, Chaplin AK (2021) The resolution revolution in X-ray diffraction, Cryo-EM and other technologies. Prog Biophys Mol Biol 160:2\u20134. https:\/\/doi.org\/10.1016\/j.pbiomolbio.2021.01.003","journal-title":"Prog Biophys Mol Biol"},{"key":"4588_CR24","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.bbagen.2017.07.020","volume":"1862","author":"K Murata","year":"2018","unstructured":"Murata K, Wolf M (2018) Cryo-electron microscopy for structural analysis of dynamic biological macromolecules. Biochim Biophys Acta\u2014Gen Subj 1862:324\u2013334. https:\/\/doi.org\/10.1016\/j.bbagen.2017.07.020","journal-title":"Biochim Biophys Acta\u2014Gen Subj"},{"key":"4588_CR25","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/nature19948","volume":"537","author":"R Fernandez-Leiro","year":"2016","unstructured":"Fernandez-Leiro R, Scheres SHW (2016) Unravelling biological macromolecules with cryo-electron microscopy. Nature 537:339\u2013346. https:\/\/doi.org\/10.1038\/nature19948","journal-title":"Nature"},{"key":"4588_CR26","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.tibs.2019.04.008","volume":"44","author":"R Danev","year":"2019","unstructured":"Danev R, Yanagisawa H, Kikkawa M (2019) Cryo-electron microscopy methodology: current aspects and future directions. Trends Biochem Sci 44:837\u2013848","journal-title":"Trends Biochem Sci"},{"key":"4588_CR27","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1146\/annurev-biochem-060614-034226","volume":"84","author":"D Elmlund","year":"2015","unstructured":"Elmlund D, Elmlund H (2015) Cryogenic electron microscopy and single-particle analysis. Annu Rev Biochem 84:499\u2013517","journal-title":"Annu Rev Biochem"},{"key":"4588_CR28","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1021\/acsinfecdis.1c00433","volume":"8","author":"R Mehra","year":"2022","unstructured":"Mehra R, Kepp KP (2022) Structure and mutations of SARS-CoV-2 spike protein: a focused overview. ACS Infect Dis 8:29\u201358. https:\/\/doi.org\/10.1021\/acsinfecdis.1c00433","journal-title":"ACS Infect Dis"},{"key":"4588_CR29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000002","author":"N Tokuriki","year":"2008","unstructured":"Tokuriki N, Stricher F, Serrano L, Tawfik DS (2008) How protein stability and new functions trade off. PLoS Comput Biol. https:\/\/doi.org\/10.1371\/journal.pcbi.1000002","journal-title":"PLoS Comput Biol"},{"key":"4588_CR30","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1002\/prot.22964","volume":"79","author":"RA Goldstein","year":"2011","unstructured":"Goldstein RA (2011) The evolution and evolutionary consequences of marginal thermostability in proteins. Proteins 79:1396\u20131407. https:\/\/doi.org\/10.1002\/prot.22964","journal-title":"Proteins"},{"key":"4588_CR31","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583520000037","author":"KP Kepp","year":"2020","unstructured":"Kepp KP (2020) Survival of the cheapest: how proteome cost minimization drives evolution. Q Rev Biophys. https:\/\/doi.org\/10.1017\/S0033583520000037","journal-title":"Q Rev Biophys"},{"key":"4588_CR32","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.jmb.2008.04.024","volume":"379","author":"S Bershtein","year":"2008","unstructured":"Bershtein S, Goldin K, Tawfik DS (2008) Intense neutral drifts yield robust and evolvable consensus proteins. J Mol Biol 379:1029\u20131044. https:\/\/doi.org\/10.1016\/j.jmb.2008.04.024","journal-title":"J Mol Biol"},{"key":"4588_CR33","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1038\/s41422-020-00430-4","volume":"30","author":"I Berger","year":"2020","unstructured":"Berger I, Schaffitzel C (2020) The SARS-CoV-2 spike protein: balancing stability and infectivity. Cell Res 30:1059\u20131060. https:\/\/doi.org\/10.1038\/s41422-020-00430-4","journal-title":"Cell Res"},{"key":"4588_CR34","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1126\/science.abd4251","volume":"369","author":"Y Cai","year":"2020","unstructured":"Cai Y, Zhang J, Xiao T et al (2020) Distinct conformational states of SARS-CoV-2 spike protein. Science 369:1586\u20131592","journal-title":"Science"},{"key":"4588_CR35","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","volume":"181","author":"AC Walls","year":"2020","unstructured":"Walls AC, Park Y-J, Tortorici MA et al (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181:281\u2013292","journal-title":"Cell"},{"key":"4588_CR36","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/s41594-020-0479-4","volume":"27","author":"R Henderson","year":"2020","unstructured":"Henderson R, Edwards RJ, Mansouri K et al (2020) Controlling the SARS-CoV-2 spike glycoprotein conformation. Nat Struct Mol Biol 27:925\u2013933. https:\/\/doi.org\/10.1038\/s41594-020-0479-4","journal-title":"Nat Struct Mol Biol"},{"key":"4588_CR37","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.abb2507","volume":"367","author":"D Wrapp","year":"2020","unstructured":"Wrapp D, Wang N, Corbett KS et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367:1260\u20131263. https:\/\/doi.org\/10.1126\/science.abb2507","journal-title":"Science"},{"key":"4588_CR38","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk3445","author":"MC Maher","year":"2022","unstructured":"Maher MC, Bartha I, Weaver S et al (2022) Predicting the mutational drivers of future SARS-CoV-2 variants of concern. Sci Transl Med. https:\/\/doi.org\/10.1126\/scitranslmed.abk3445","journal-title":"Sci Transl Med"},{"key":"4588_CR39","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe5575","author":"C Xu","year":"2021","unstructured":"Xu C, Wang Y, Liu C et al (2021) Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. Sci Adv. https:\/\/doi.org\/10.1126\/sciadv.abe5575","journal-title":"Sci Adv"},{"key":"4588_CR40","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s10822-016-9914-3","volume":"30","author":"S Kulshreshtha","year":"2016","unstructured":"Kulshreshtha S, Chaudhary V, Goswami GK, Mathur N (2016) Computational approaches for predicting mutant protein stability. J Comput Aided Mol Des 30:401\u2013412","journal-title":"J Comput Aided Mol Des"},{"key":"4588_CR41","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1093\/bioinformatics\/bty979","volume":"35","author":"L Montanucci","year":"2019","unstructured":"Montanucci L, Savojardo C, Martelli PL et al (2019) On the biases in predictions of protein stability changes upon variations: the INPS test case. Bioinformatics 35:2525\u20132527","journal-title":"Bioinformatics"},{"key":"4588_CR42","doi-asserted-by":"publisher","first-page":"3659","DOI":"10.1093\/bioinformatics\/bty348","volume":"34","author":"F Pucci","year":"2018","unstructured":"Pucci F, Bernaerts KV, Kwasigroch JM, Rooman M (2018) Quantification of biases in predictions of protein stability changes upon mutations. Bioinformatics 34:3659\u20133665. https:\/\/doi.org\/10.1093\/bioinformatics\/bty348","journal-title":"Bioinformatics"},{"key":"4588_CR43","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/protein\/gzp030","volume":"22","author":"V Potapov","year":"2009","unstructured":"Potapov V, Cohen M, Schreiber G (2009) Assessing computational methods for predicting protein stability upon mutation: good on average but not in the details. Protein Eng Des Sel 22:553\u2013560. https:\/\/doi.org\/10.1093\/protein\/gzp030","journal-title":"Protein Eng Des Sel"},{"key":"4588_CR44","doi-asserted-by":"publisher","first-page":"W215","DOI":"10.1093\/nar\/gkr363","volume":"39","author":"CL Worth","year":"2011","unstructured":"Worth CL, Preissner R, Blundell TL (2011) SDM\u2013a server for predicting effects of mutations on protein stability and malfunction. Nucleic Acids Res 39:W215\u2013W222. https:\/\/doi.org\/10.1093\/nar\/gkr363","journal-title":"Nucleic Acids Res"},{"key":"4588_CR45","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/bioinformatics\/btt691","volume":"30","author":"DEV Pires","year":"2014","unstructured":"Pires DEV, Ascher DB, Blundell TL (2014) MCSM: Predicting the effects of mutations in proteins using graph-based signatures. Bioinformatics 30:335\u2013342. https:\/\/doi.org\/10.1093\/bioinformatics\/btt691","journal-title":"Bioinformatics"},{"key":"4588_CR46","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1093\/bioinformatics\/btp445","volume":"25","author":"Y Dehouck","year":"2009","unstructured":"Dehouck Y, Grosfils A, Folch B et al (2009) Fast and accurate predictions of protein stability changes upon mutations using statistical potentials and neural networks: PoPMuSiC-2.0. Bioinformatics 25:2537\u20132543. https:\/\/doi.org\/10.1093\/bioinformatics\/btp445","journal-title":"Bioinformatics"},{"key":"4588_CR47","doi-asserted-by":"publisher","first-page":"W306","DOI":"10.1093\/nar\/gki375","volume":"33","author":"E Capriotti","year":"2005","unstructured":"Capriotti E, Fariselli P, Casadio R (2005) I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Res 33:W306\u2013W310","journal-title":"Nucleic Acids Res"},{"key":"4588_CR48","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.cell.2022.01.001","volume":"185","author":"P Han","year":"2022","unstructured":"Han P, Li L, Liu S et al (2022) Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2. Cell 185:630\u2013640","journal-title":"Cell"},{"key":"4588_CR49","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.sbi.2021.11.001","volume":"72","author":"F Pucci","year":"2022","unstructured":"Pucci F, Schwersensky M, Rooman M (2022) Artificial intelligence challenges for predicting the impact of mutations on protein stability. Curr Opin Struct Biol 72:161\u2013168. https:\/\/doi.org\/10.1016\/j.sbi.2021.11.001","journal-title":"Curr Opin Struct Biol"},{"key":"4588_CR50","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/978-1-0716-2095-3_6","volume-title":"Data Min Tech Life Sci","author":"R Casadio","year":"2022","unstructured":"Casadio R, Savojardo C, Fariselli P et al (2022) Turning failures into applications: The problem of protein \u0394\u0394G prediction. In: Carugo Oliviero, Eisenhaber Frank (eds) Data Min Tech Life Sci. Springer, Berlin, pp 169\u2013185"},{"key":"4588_CR51","doi-asserted-by":"publisher","first-page":"4772","DOI":"10.1021\/acs.jcim.0c00591","volume":"60","author":"O Caldararu","year":"2020","unstructured":"Caldararu O, Mehra R, Blundell TL, Kepp KP (2020) Systematic investigation of the data set dependency of protein stability predictors. J Chem Inf Model 60:4772\u20134784. https:\/\/doi.org\/10.1021\/acs.jcim.0c00591","journal-title":"J Chem Inf Model"},{"key":"4588_CR52","doi-asserted-by":"publisher","first-page":"3028","DOI":"10.1021\/ci300398z","volume":"52","author":"NJ Christensen","year":"2012","unstructured":"Christensen NJ, Kepp KP (2012) Accurate stabilities of laccase mutants predicted with a modified FoldX protocol. J Chem Inf Model 52:3028\u20133042. https:\/\/doi.org\/10.1021\/ci300398z","journal-title":"J Chem Inf Model"},{"key":"4588_CR53","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1021\/jp4119138","volume":"118","author":"KP Kepp","year":"2014","unstructured":"Kepp KP (2014) Computing stability effects of mutations in human superoxide dismutase 1. J Phys Chem B 118:1799\u20131812. https:\/\/doi.org\/10.1021\/jp4119138","journal-title":"J Phys Chem B"},{"key":"4588_CR54","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.bbapap.2015.06.002","volume":"1854","author":"KP Kepp","year":"2015","unstructured":"Kepp KP (2015) Towards a \u201cGolden Standard\u201d for computing globin stability: stability and structure sensitivity of myoglobin mutants. Biochim Biophys Acta 1854:1239\u20131248. https:\/\/doi.org\/10.1016\/j.bbapap.2015.06.002","journal-title":"Biochim Biophys Acta"},{"key":"4588_CR55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046084","author":"G Thiltgen","year":"2012","unstructured":"Thiltgen G, Goldstein RA (2012) Assessing predictors of changes in protein stability upon mutation using self-consistency. PLoS ONE. https:\/\/doi.org\/10.1371\/journal.pone.0046084","journal-title":"PLoS ONE"},{"key":"4588_CR56","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","volume":"182","author":"TN Starr","year":"2020","unstructured":"Starr TN, Greaney AJ, Hilton SK et al (2020) Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 182:1295\u20131310","journal-title":"Cell"},{"key":"4588_CR57","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1021\/acs.jcim.8b00697","volume":"59","author":"H Cao","year":"2019","unstructured":"Cao H, Wang J, He L et al (2019) DeepDDG: predicting the stability change of protein point mutations using neural networks. J Chem Inf Model 59:1508\u20131514","journal-title":"J Chem Inf Model"},{"key":"4588_CR58","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/jcc.26810","volume":"43","author":"KT B\u00e6k","year":"2022","unstructured":"B\u00e6k KT, Kepp KP (2022) Data set and fitting dependencies when estimating protein mutant stability: toward simple, balanced, and interpretable models. J Comput Chem 43:504\u2013518. https:\/\/doi.org\/10.1002\/jcc.26810","journal-title":"J Comput Chem"},{"key":"4588_CR59","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12859-021-04030-w","volume":"22","author":"O Caldararu","year":"2021","unstructured":"Caldararu O, Blundell TL, Kepp KP (2021) A base measure of precision for protein stability predictors: structural sensitivity. BMC Bioinformatics 22:88. https:\/\/doi.org\/10.1186\/s12859-021-04030-w","journal-title":"BMC Bioinformatics"},{"key":"4588_CR60","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1021\/acsomega.0c03512","volume":"6","author":"NG Herrera","year":"2021","unstructured":"Herrera NG, Morano NC, Celikgil A et al (2021) Characterization of the SARS-CoV-2 S protein: biophysical, biochemical, structural, and antigenic analysis. ACS Omega 6:85\u2013102. https:\/\/doi.org\/10.1021\/acsomega.0c03512","journal-title":"ACS Omega"},{"key":"4588_CR61","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/s41594-020-0483-8","volume":"27","author":"M McCallum","year":"2020","unstructured":"McCallum M, Walls AC, Bowen JE et al (2020) Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation. Nat Struct Mol Biol 27:942\u2013949. https:\/\/doi.org\/10.1038\/s41594-020-0483-8","journal-title":"Nat Struct Mol Biol"},{"key":"4588_CR62","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.chom.2020.06.010","volume":"28","author":"J Huo","year":"2020","unstructured":"Huo J, Zhao Y, Ren J et al (2020) Neutralization of SARS-CoV-2 by destruction of the prefusion spike. Cell Host Microbe 28:445-454.e6. https:\/\/doi.org\/10.1016\/j.chom.2020.06.010","journal-title":"Cell Host Microbe"},{"key":"4588_CR63","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1126\/science.abd3255","volume":"370","author":"C Toelzer","year":"2020","unstructured":"Toelzer C, Gupta K, Yadav SKN et al (2020) Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein. Science 370:725\u2013730. https:\/\/doi.org\/10.1126\/science.abd3255","journal-title":"Science"},{"key":"4588_CR64","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1126\/science.abc5881","volume":"369","author":"Z Lv","year":"2020","unstructured":"Lv Z, Deng Y-Q, Ye Q et al (2020) Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Science 369:1505\u20131509. https:\/\/doi.org\/10.1126\/science.abc5881","journal-title":"Science"},{"key":"4588_CR65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-20314-w","volume":"12","author":"C Zhang","year":"2021","unstructured":"Zhang C, Wang Y, Zhu Y et al (2021) Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. Nat Commun 12:1\u201316","journal-title":"Nat Commun"},{"key":"4588_CR66","unstructured":"Schr\u00f6dinger Release 2022-3: Maestro, Schr\u00f6dinger, LLC, New York, NY (2021)"},{"key":"4588_CR67","doi-asserted-by":"publisher","DOI":"10.1268\/f1000research.7931.1","author":"S Mitternacht","year":"2016","unstructured":"Mitternacht S (2016) FreeSASA an open source C library for solvent accessible surface area calculations. F1000Res. https:\/\/doi.org\/10.1268\/f1000research.7931.1","journal-title":"F1000Res"},{"key":"4588_CR68","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1073\/pnas.0905481107","volume":"107","author":"A Meents","year":"2010","unstructured":"Meents A, Gutmann S, Wagner A, Schulze-Briese C (2010) Origin and temperature dependence of radiation damage in biological samples at cryogenic temperatures. Proc Natl Acad Sci 107:1094\u20131099","journal-title":"Proc Natl Acad Sci"},{"key":"4588_CR69","doi-asserted-by":"publisher","first-page":"5427","DOI":"10.1039\/C9CP06723J","volume":"22","author":"R Mehra","year":"2020","unstructured":"Mehra R, Dehury B, Kepp KP (2020) Cryo-temperature effects on membrane protein structure and dynamics. Phys Chem Chem Phys 22:5427\u20135438","journal-title":"Phys Chem Chem Phys"},{"key":"4588_CR70","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s10858-011-9535-z","volume":"51","author":"AH Linden","year":"2011","unstructured":"Linden AH, Franks WT, Akbey \u00dc et al (2011) Cryogenic temperature effects and resolution upon slow cooling of protein preparations in solid state NMR. J Biomol NMR 51:283\u2013292. https:\/\/doi.org\/10.1007\/s10858-011-9535-z","journal-title":"J Biomol NMR"},{"key":"4588_CR71","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1021\/bi00124a006","volume":"31","author":"RF Tilton Jr","year":"1992","unstructured":"Tilton RF Jr, Dewan JC, Petsko GA (1992) Effects of temperature on protein structure and dynamics: X-ray crystallographic studies of the protein ribonuclease-a at nine different temperatures from 98 to 320K. Biochemistry 31:2469\u20132481","journal-title":"Biochemistry"},{"key":"4588_CR72","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/S0006-3495(86)83455-5","volume":"50","author":"W Doster","year":"1986","unstructured":"Doster W, Bachleitner A, Dunau R et al (1986) Thermal properties of water in myoglobin crystals and solutions at subzero temperatures. Biophys J 50:213\u2013219. https:\/\/doi.org\/10.1016\/S0006-3495(86)83455-5","journal-title":"Biophys J"},{"key":"4588_CR73","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1107\/S0907444904027179","volume":"61","author":"KV Dunlop","year":"2005","unstructured":"Dunlop KV, Irvin RT, Hazes B (2005) Pros and cons of cryocrystallography: should we also collect a room-temperature data set? Acta Crystallogr Sect D Biol Crystallogr 61:80\u201387","journal-title":"Acta Crystallogr Sect D Biol Crystallogr"},{"key":"4588_CR74","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s41594-020-00547-5","volume":"28","author":"RJ Edwards","year":"2021","unstructured":"Edwards RJ, Mansouri K, Stalls V et al (2021) Cold sensitivity of the SARS-CoV-2 spike ectodomain. Nat Struct Mol Biol 28:128\u2013131","journal-title":"Nat Struct Mol Biol"},{"key":"4588_CR75","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1016\/j.jmb.2007.03.069","volume":"369","author":"N Tokuriki","year":"2007","unstructured":"Tokuriki N, Stricher F, Schymkowitz J et al (2007) The stability effects of protein mutations appear to be universally distributed. J Mol Biol 369:1318\u20131332. https:\/\/doi.org\/10.1016\/j.jmb.2007.03.069","journal-title":"J Mol Biol"},{"key":"4588_CR76","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1002\/jmv.25754","volume":"92","author":"M Kandeel","year":"2020","unstructured":"Kandeel M, Ibrahim A, Fayez M, Al-Nazawi M (2020) From SARS and MERS CoVs to SARS-CoV-2: Moving toward more biased codon usage in viral structural and nonstructural genes. J Med Virol 92:660\u2013666. https:\/\/doi.org\/10.1002\/jmv.25754","journal-title":"J Med Virol"},{"key":"4588_CR77","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/nrm.2017.91","volume":"19","author":"G Hanson","year":"2018","unstructured":"Hanson G, Coller J (2018) Codon optimality, bias and usage in translation and mRNA decay. Nat Rev Mol cell Biol 19:20\u201330","journal-title":"Nat Rev Mol cell Biol"},{"key":"4588_CR78","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1021\/acs.jcim.1c00201","volume":"61","author":"O Caldararu","year":"2021","unstructured":"Caldararu O, Blundell TL, Kepp KP (2021) Three simple properties explain protein stability change upon mutation. J Chem Inf Model 61:1981\u20131988","journal-title":"J Chem Inf Model"},{"key":"4588_CR79","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100902","author":"CT Barrett","year":"2021","unstructured":"Barrett CT, Neal HE, Edmonds K et al (2021) Effect of clinical isolate or cleavage site mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell-cell fusion. J Biol Chem. https:\/\/doi.org\/10.1016\/j.jbc.2021.100902","journal-title":"J Biol Chem"},{"key":"4588_CR80","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1093\/bib\/bbaa233","volume":"22","author":"S Teng","year":"2021","unstructured":"Teng S, Sobitan A, Rhoades R et al (2021) Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity. Brief Bioinform 22:1239\u20131253. https:\/\/doi.org\/10.1093\/bib\/bbaa233","journal-title":"Brief Bioinform"},{"key":"4588_CR81","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.765039","author":"T Mohammad","year":"2021","unstructured":"Mohammad T, Choudhury A, Habib I et al (2021) Genomic variations in the structural proteins of SARS-CoV-2 and their deleterious impact on pathogenesis: a comparative genomics approach. Front Cell Infect Microbiol. https:\/\/doi.org\/10.3389\/fcimb.2021.765039","journal-title":"Front Cell Infect Microbiol"},{"key":"4588_CR82","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1021\/acscentsci.0c01056","volume":"6","author":"L Casalino","year":"2020","unstructured":"Casalino L, Gaieb Z, Goldsmith JA et al (2020) Beyond shielding: the roles of Glycans in the SARS-CoV-2 spike protein. ACS Cent Sci 6:1722\u20131734. https:\/\/doi.org\/10.1021\/acscentsci.0c01056","journal-title":"ACS Cent Sci"},{"key":"4588_CR83","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/nrg2452","volume":"9","author":"PC Phillips","year":"2008","unstructured":"Phillips PC (2008) Epistasis\u2014the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet 9:855\u2013867","journal-title":"Nat Rev Genet"},{"key":"4588_CR84","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00262-0","author":"M Ramanathan","year":"2021","unstructured":"Ramanathan M, Ferguson ID, Miao W, Khavari PA (2021) SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. Lancet Infect Dis. https:\/\/doi.org\/10.1016\/S1473-3099(21)00262-0","journal-title":"Lancet Infect Dis"},{"key":"4588_CR85","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1126\/science.abn7760","volume":"375","author":"D Mannar","year":"2022","unstructured":"Mannar D, Saville JW, Zhu X et al (2022) SARS-CoV-2 Omicron variant: antibody evasion and cryo-EM structure of spike protein ACE2 complex. Science 375:760\u2013764. https:\/\/doi.org\/10.1126\/science.abn7760","journal-title":"Science"},{"key":"4588_CR86","doi-asserted-by":"publisher","first-page":"16152","DOI":"10.1073\/pnas.0705366104","volume":"104","author":"KB Zeldovich","year":"2007","unstructured":"Zeldovich KB, Chen P, Shakhnovich EI (2007) Protein stability imposes limits on organism complexity and speed of molecular evolution. Proc Natl Acad Sci U S A 104:16152\u201316157. https:\/\/doi.org\/10.1073\/pnas.0705366104","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4588_CR87","doi-asserted-by":"publisher","first-page":"2956","DOI":"10.1093\/gbe\/evu223","volume":"6","author":"P Dasmeh","year":"2014","unstructured":"Dasmeh P, Serohijos AWR, Kepp KP, Shakhnovich EI (2014) The influence of selection for protein stability on dN\/dS estimations. Genome Biol Evol 6:2956\u20132967. https:\/\/doi.org\/10.1093\/gbe\/evu223","journal-title":"Genome Biol Evol"},{"key":"4588_CR88","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.chom.2020.11.007","volume":"29","author":"AJ Greaney","year":"2021","unstructured":"Greaney AJ, Starr TN, Gilchuk P et al (2021) Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host Microbe 29:44\u201357","journal-title":"Cell Host Microbe"},{"key":"4588_CR89","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100255","volume":"2","author":"TN Starr","year":"2021","unstructured":"Starr TN, Greaney AJ, Dingens AS, Bloom JD (2021) Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016. Cell Reports Med 2:100255","journal-title":"Cell Reports Med"},{"key":"4588_CR90","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.1002\/anie.201207842","volume":"52","author":"MT Reetz","year":"2013","unstructured":"Reetz MT (2013) The importance of additive and non-additive mutational effects in protein engineering. Angew Chemie Int Ed 52:2658\u20132666","journal-title":"Angew Chemie Int Ed"},{"key":"4588_CR91","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nature11510","volume":"490","author":"MS Breen","year":"2012","unstructured":"Breen MS, Kemena C, Vlasov PK et al (2012) Epistasis as the primary factor in molecular evolution. Nature 490:535\u2013538","journal-title":"Nature"},{"key":"4588_CR92","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/nbt.3769","volume":"35","author":"TA Hopf","year":"2017","unstructured":"Hopf TA, Ingraham JB, Poelwijk FJ et al (2017) Mutation effects predicted from sequence co-variation. Nat Biotechnol 35:128\u2013135. https:\/\/doi.org\/10.1038\/nbt.3769","journal-title":"Nat Biotechnol"},{"key":"4588_CR93","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00135-22","author":"ND Rochman","year":"2022","unstructured":"Rochman ND, Faure G, Wolf YI et al (2022) Epistasis at the SARS-CoV-2 receptor-binding domain interface and the propitiously boring implications for vaccine escape. MBio. https:\/\/doi.org\/10.1128\/mbio.00135-22","journal-title":"MBio"}],"container-title":["Molecular and Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-022-04588-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11010-022-04588-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-022-04588-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T14:04:08Z","timestamp":1683381848000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11010-022-04588-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,27]]},"references-count":93,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["4588"],"URL":"https:\/\/doi.org\/10.1007\/s11010-022-04588-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.03.21.485157","asserted-by":"object"}]},"ISSN":["0300-8177","1573-4919"],"issn-type":[{"value":"0300-8177","type":"print"},{"value":"1573-4919","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,27]]},"assertion":[{"value":"21 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors declare no conflicts of interest, financial or otherwise, associated with this work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}