{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:57:52Z","timestamp":1781287072426,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012964","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009227","name":"Iowa State University","doi-asserted-by":"publisher","award":["Startup Grant; Building a World of Difference Faculty Fellow"],"award-info":[{"award-number":["Startup Grant; Building a World of Difference Faculty Fellow"]}],"id":[{"id":"10.13039\/100009227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009227","name":"Iowa State University","doi-asserted-by":"publisher","award":["CIRAS Mini Grant"],"award-info":[{"award-number":["CIRAS Mini Grant"]}],"id":[{"id":"10.13039\/100009227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DQDBM7FGJPC5"],"award-info":[{"award-number":["DQDBM7FGJPC5"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>A generalizable computational platform, CTRL-V (Computational TRacking of Likely Variants), is introduced to design selective binding (dual bait) biosensor proteins. The iteratively evolving receptor binding domain (RBD) of SARS-CoV-2 spike protein has been construed as a model dual bait biosensor which has iteratively evolved to distinguish and selectively bind to human entry receptors and avoid binding neutralizing antibodies. Spike RBD prioritizes mutations that reduce antibody binding while enhancing\/ retaining binding with the ACE2 receptor. CTRL-V\u2019s through iterative design cycles was shown to pinpoint 20% (of the 39) reported SARS-CoV-2 point mutations across 30 circulating, infective strains as responsible for immune escape from commercial antibody LY-CoV1404. CTRL-V successfully identifies ~70% (five out of seven) single point mutations (371F, 373P, 440K, 445H, 456L) in the latest circulating KP.2 variant and offers detailed structural insights to the escape mechanism. While other data-driven viral escape variant predictor tools have shown promise in predicting potential future viral variants, they require massive amounts of data to bypass the need for physics of explicit biochemical interactions. Consequently, they cannot be generalized for other protein design applications. The publicly availably viral escape data was leveraged as <jats:italic>in vivo<\/jats:italic> anchors to streamline a computational workflow that can be generalized for dual bait biosensor design tasks as exemplified by identifying key mutational loci in Raf kinase that enables it to selectively bind Ras and Rap1a GTP. We demonstrate three versions of CTRL-V which use a combination of integer optimization, stochastic sampling by PyRosetta, and deep learning-based ProteinMPNN for structure-guided biosensor design.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012964","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T17:40:33Z","timestamp":1744738833000},"page":"e1012964","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Viral escape-inspired framework for structure-guided dual bait protein biosensor design"],"prefix":"10.1371","volume":"21","author":[{"given":"Yee Chuen","family":"Teoh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Sakib","family":"Noor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9476-548X","authenticated-orcid":true,"given":"Sina","family":"Aghakhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Girton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4522-6911","authenticated-orcid":true,"given":"Ratul","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"issue":"1","key":"pcbi.1012964.ref001","doi-asserted-by":"crossref","first-page":"4998","DOI":"10.1038\/s41598-022-26951-z","article-title":"Reshaping healthcare with wearable biosensors","volume":"13","author":"AA Smith","year":"2023","journal-title":"Sci Rep"},{"issue":"3","key":"pcbi.1012964.ref002","doi-asserted-by":"crossref","first-page":"188726","DOI":"10.1016\/j.bbcan.2022.188726","article-title":"Biosensors as diagnostic tools in clinical applications","author":"C Lino","year":"2022","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"2","key":"pcbi.1012964.ref003","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3390\/foods13020235","article-title":"Intelligent Biosensors Promise Smarter Solutions in Food Safety 4.0","volume":"13","author":"Y Chen","year":"2024","journal-title":"Foods"},{"key":"pcbi.1012964.ref004","doi-asserted-by":"crossref","first-page":"gzaa027","DOI":"10.1093\/protein\/gzaa027","article-title":"Engineering sensitivity and specificity of AraC-based biosensors responsive to triacetic acid lactone and orsellinic acid","volume":"33","author":"Z Wang","year":"2020","journal-title":"Protein Eng Des Sel"},{"issue":"11","key":"pcbi.1012964.ref005","doi-asserted-by":"crossref","first-page":"e00694-19","DOI":"10.1128\/AEM.00694-19","article-title":"Sensitive and Specific Whole-Cell Biosensor for Arsenic Detection","volume":"85","author":"X Jia","year":"2019","journal-title":"Appl Environ Microbiol"},{"issue":"24","key":"pcbi.1012964.ref006","doi-asserted-by":"crossref","first-page":"17080","DOI":"10.1074\/jbc.274.24.17080","article-title":"A two-hybrid dual bait system to discriminate specificity of protein interactions","volume":"274","author":"I Serebriiskii","year":"1999","journal-title":"J Biol Chem"},{"key":"pcbi.1012964.ref007","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1016\/j.csbj.2020.09.019","article-title":"Computational biophysical characterization of the SARS-CoV-2 spike protein binding with the ACE2 receptor and implications for infectivity","volume":"18","author":"R Chowdhury","year":"2020","journal-title":"Comput Struct Biotechnol J"},{"key":"pcbi.1012964.ref008","author":"Worldometer","year":"2023"},{"key":"pcbi.1012964.ref009","unstructured":"Center on Budget and Policy Priorities. Tracking the COVID-19 recession\u2019s effects on food, housing, and employment. 2022."},{"issue":"6516","key":"pcbi.1012964.ref010","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1126\/science.abc8169","article-title":"The emergence of SARS-CoV-2 in Europe and North America","volume":"370","author":"M Worobey","year":"2020","journal-title":"Science"},{"key":"pcbi.1012964.ref011","unstructured":"Hodcroft E. Covariants.org. 2024."},{"key":"pcbi.1012964.ref012","unstructured":"COVID-19 variants | WHO COVID-19 dashboard. n.d."},{"issue":"11","key":"pcbi.1012964.ref013","doi-asserted-by":"crossref","first-page":"961","DOI":"10.3349\/ymj.2021.62.11.961","article-title":"SARS-CoV-2 Variants of Concern","volume":"62","author":"JY Choi","year":"2021","journal-title":"Yonsei Med J"},{"issue":"24","key":"pcbi.1012964.ref014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2807\/1560-7917.ES.2021.26.24.2100509","article-title":"Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021","volume":"26","author":"F Campbell","year":"2021","journal-title":"Eurosurveillance"},{"issue":"7902","key":"pcbi.1012964.ref015","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41586-022-04411-y","article-title":"Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa","volume":"603","author":"R Viana","year":"2022","journal-title":"Nature"},{"key":"pcbi.1012964.ref016","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa2119451","article-title":"Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant","volume":"386","author":"N Andrews","year":"2022","journal-title":"New England Journal of Medicine"},{"issue":"10332","key":"pcbi.1012964.ref017","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/S0140-6736(22)00462-7","article-title":"Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study","volume":"399","author":"T Nyberg","year":"2022","journal-title":"Lancet"},{"issue":"5","key":"pcbi.1012964.ref018","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.bpj.2016.02.006","article-title":"How Viruses Invade Cells","volume":"110","author":"FS Cohen","year":"2016","journal-title":"Biophys J"},{"key":"pcbi.1012964.ref019","first-page":"Page range needed","article-title":"Introduction to T and B Lymphocytes","author":"R Cano","year":"n.d","journal-title":"Autoimmunity from bench to bedside"},{"key":"pcbi.1012964.ref020","doi-asserted-by":"crossref","unstructured":"Carter D. 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Wu","year":"2022"},{"issue":"11","key":"pcbi.1012964.ref027","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/s41587-022-01432-w","article-title":"Single-sequence protein structure prediction using a language model and deep learning","volume":"40","author":"R Chowdhury","year":"2022","journal-title":"Nat Biotechnol"},{"issue":"6526","key":"pcbi.1012964.ref028","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1126\/science.abd7331","article-title":"Learning the language of viral evolution and escape","volume":"371","author":"B Hie","year":"2021","journal-title":"Science"},{"issue":"7984","key":"pcbi.1012964.ref029","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41586-023-06617-0","article-title":"Learning from prepandemic data to forecast viral escape","volume":"622","author":"NN Thadani","year":"2023","journal-title":"Nature"},{"key":"pcbi.1012964.ref030","first-page":"1","article-title":"The prediction of virus mutation using neural networks 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Lilly\u2019s bebtelovimab receives Emergency Use Authorization for the treatment of mild-to-moderate COVID-19. 2022."},{"key":"pcbi.1012964.ref043","unstructured":"United States Food and Drug Adminstration. Bebtelovimab FAQs 08182022. 2022 Aug."},{"key":"pcbi.1012964.ref044","author":"Eli Lily and Company","year":"11 Feb 2022"},{"key":"pcbi.1012964.ref045","unstructured":"FDA. Frequently Asked Questions on the Emergency Use Authorization of Bebtelovimab for the Treatment of COVID-19. 2022 Aug."},{"key":"pcbi.1012964.ref046","author":"FDA","year":"2022"},{"issue":"2","key":"pcbi.1012964.ref047","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/prot.26422","article-title":"De novo design and Rosetta-based assessment of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike receptor binding domain (RBD)","volume":"91","author":"VS Boorla","year":"2023","journal-title":"Proteins"},{"issue":"9","key":"pcbi.1012964.ref048","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41573-022-00495-3","article-title":"Antibodies to combat viral infections: development strategies and progress","volume":"21","author":"G Pantaleo","year":"2022","journal-title":"Nat Rev Drug 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Furukawa","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"7","key":"pcbi.1012964.ref052","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.3390\/v14071451","article-title":"Human ACE2 Polymorphisms from Different Human Populations Modulate SARS-CoV-2 Infection","volume":"14","author":"P Hu","year":"2022","journal-title":"Viruses"},{"key":"pcbi.1012964.ref053","article-title":"Evaluating the performance of protein structure prediction in detecting structural changes of pathogenic nonsynonymous single nucleotide variants","author":"H-S Lai","year":"2023"},{"issue":"4","key":"pcbi.1012964.ref054","first-page":"603","article-title":"Amino acid interaction preferences in proteins","volume":"19","author":"A Jha","year":"2010","journal-title":"Protein Science"},{"issue":"1","key":"pcbi.1012964.ref055","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","article-title":"A simple method for displaying the hydropathic character of a 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Dauparas","year":"2022","journal-title":"Science"},{"issue":"6637","key":"pcbi.1012964.ref066","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1126\/science.ade2574","article-title":"Evolutionary-scale prediction of atomic-level protein structure with a language model","volume":"379","author":"Z Lin","year":"2023","journal-title":"Science"},{"issue":"7","key":"pcbi.1012964.ref067","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"HADDOCK: a protein-protein docking approach based on biochemical or biophysical information","volume":"125","author":"C Dominguez","year":"2003","journal-title":"J Am Chem Soc"},{"key":"pcbi.1012964.ref068","article-title":"HADDOCK3","author":"Bonvin\u2019s Lab","year":"2022"},{"issue":"5","key":"pcbi.1012964.ref069","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1093\/bioinformatics\/btq007","article-title":"PyRosetta: a script-based interface for implementing molecular modeling algorithms using 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