{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:13:14Z","timestamp":1788437594699,"version":"build-2803163510"},"reference-count":51,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/na","name":"Ministry of Science and Technology of Vietnam","doi-asserted-by":"publisher","award":["NDT\/DE\/21\/28"],"award-info":[{"award-number":["NDT\/DE\/21\/28"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Botulism is a potentially fatal illness in humans and many animals caused by the botulinum neurotoxins (BoNTs) produced mainly by Clostridium botulinum, which can be found in a wide variety of foods. The treatment of this illness requires antitoxin drugs given to the patients within a 48 h window to be effective. Therefore, there is a strong need for the development of rapid and sensitive biosensors for the early detection of the toxins in foods. In this work, by using comprehensive atomistic computer modeling and simulation, we investigate aptamers that bind BoNT serotypes A, B, and C to serve as recognition elements in the biosensor design for cross-serotype detection. Known aptamers targeting BoNT\/A and BoNT\/C are investigated in this work to understand whether they can cross-react with other serotypes. Our results highlight the importance of structural relaxation of the aptamers, which the standard docking procedure cannot adequately capture. During molecular dynamics, most of the aptamer structural relaxation correlates with binding to the toxins. Among the aptamers chosen, we found two aptamers A4 and A5 that bind equally strongly to all serotypes. C5 binds equally strongly to its designated target of serotype C, but it binds significantly weaker to other serotypes. These most promising aptamers, based on the computational analyses, are all ssDNA aptamers and share a common feature of a DNA double helix of 5\u20136 nucleotide base pairs. For all aptamers investigated, there are two binding sites for an aptamer on BoNT, which are located on opposite sides of the protein. This suggests an experimental setup of a sandwich array to allow aptamers to bind to both binding sites for optimal sensitivities. Our computational results provide molecular mechanisms of binding and assist in further optimization and design of new aptamers for these botulinum neurotoxins.<\/jats:p>","DOI":"10.1021\/acsomega.6c06201","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T01:01:33Z","timestamp":1787187693000},"page":"51792-51804","source":"Crossref","is-referenced-by-count":0,"title":["Toward an Aptamer-Based\nBiosensor for Cross-Serotype\nDetection of Botulinum Neurotoxin: Binding Mechanism from a Comprehensive\nComputational Investigation"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9813-3359","authenticated-orcid":true,"given":"Ly Hai","family":"Nguyen","sequence":"first","affiliation":[{"name":"Duy Tan University , , 1 Phung Chi Kien , Cau Giay, ,","place":["Hanoi, Vietnam, 11300"]},{"name":"Duy Tan University , , ,","place":["Da Nang, Vietnam, 50000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien Thi Ngoc","family":"Truong","sequence":"additional","affiliation":[{"name":"Hoa Lac High-Tech Park , , km29 Thang Long Boulevard , ,","place":["Hanoi, Vietnam, 13100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3788-8731","authenticated-orcid":true,"given":"Phi Long","family":"Nguyen","sequence":"additional","affiliation":[{"name":"VinUniversity , , Gia Lam , ,","place":["Hanoi, Vietnam, 12400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quynh","family":"Luu-Manh","sequence":"additional","affiliation":[{"name":"University of Science, Vietnam National University - Hanoi , , 334 Nguyen Trai , Thanh Xuan, ,","place":["Hanoi, Vietnam, 11400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen Bao","family":"Pham","sequence":"additional","affiliation":[{"name":"University of Science, Vietnam National University - Hanoi , , 334 Nguyen Trai , Thanh Xuan, ,","place":["Hanoi, Vietnam, 11400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-2538","authenticated-orcid":true,"given":"Thi Viet Bac","family":"Phung","sequence":"additional","affiliation":[{"name":"VinUniversity , , Gia Lam , ,","place":["Hanoi, Vietnam, 12400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6331-2453","authenticated-orcid":true,"given":"Toan The","family":"Nguyen","sequence":"additional","affiliation":[{"name":"University of Science, Vietnam National University - Hanoi , , 334 Nguyen Trai , Thanh Xuan, ,","place":["Hanoi, Vietnam, 11400"]},{"name":"University of Science, Vietnam National University - Hanoi , , 334 Nguyen Trai , Thanh Xuan, ,","place":["Hanoi, Vietnam, 11400"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"2026090307182778200_cit1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1128\/mr.46.1.86-94.1982","article-title":"Bacterial\ntoxins: a table of lethal amounts","volume":"46","author":"Gill","year":"1982","journal-title":"Microbiol.\nRev."},{"key":"2026090307182778200_cit2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jns.2005.04.017","article-title":"Expanding use of\nbotulinum toxin","volume":"235","author":"Bhidayasiri","year":"2005","journal-title":"J. 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Microbiol."},{"key":"2026090307182778200_cit6","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1093\/infdis\/jiv327","article-title":"A Novel Botulinum Neurotoxin, Previously Reported as\nSerotype H, Has a Hybrid-Like Structure With Regions of Similarity\nto the Structures of Serotypes A and F and Is Neutralized With Serotype\nA Antitoxin","volume":"213","author":"Maslanka","year":"2016","journal-title":"J. Infect. 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Rep."},{"key":"2026090307182778200_cit28","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/toxins13010010","article-title":"Detection of active\nbont\/c and d\nby endopep-ms using maldi biotyper instrument and comparison with\nthe mouse test bioassay","volume":"13","author":"Drigo","year":"2021","journal-title":"Toxins"},{"key":"2026090307182778200_cit29","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3390\/bios10080098","article-title":"Docking\nsimulation and sandwich assay for aptamer-based botulinum neurotoxin\ntype c detection","volume":"10","author":"Oh","year":"2020","journal-title":"Biosensors"},{"key":"2026090307182778200_cit30","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1016\/j.bbrc.2010.05.006","article-title":"In vitro selection\nof rna aptamers\nthat inhibit the activity of type a botulinum neurotoxin","volume":"396","author":"Chang","year":"2010","journal-title":"Biochem. Biophys. Res. 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Biol."},{"key":"2026090307182778200_cit36","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1093\/bioinformatics\/btz087","article-title":"G4hunter web application: a web server\nfor g-quadruplex prediction","volume":"35","author":"Bra\u0301zda","year":"2019","journal-title":"Bioinformatics"},{"key":"2026090307182778200_cit37","doi-asserted-by":"publisher","first-page":"4019","DOI":"10.1021\/bi2001483","article-title":"Structural characterization of three novel hydroxamate-based\nzinc chelating inhibitors of the clostridium botulinum serotype a\nneurotoxin light chain metalloprotease reveals a compact binding site\nresulting from 60\/70 loop flexibility","volume":"50","author":"Thompson","year":"2011","journal-title":"Biochemistry"},{"key":"2026090307182778200_cit38","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/77997","article-title":"Cocrystal structure\nof synaptobrevin-ii bound to botulinum\nneurotoxin type b at 2.0 \u00e5 resolution","volume":"7","author":"Hanson","year":"2000","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2026090307182778200_cit39","doi-asserted-by":"publisher","first-page":"10685","DOI":"10.1021\/bi701162d","article-title":"Structural and biochemical\nstudies of botulinum neurotoxin\nserotype c1 light chain protease: implications for dual substrate\nspecificity","volume":"46","author":"Jin","year":"2007","journal-title":"Biochemistry"},{"key":"2026090307182778200_cit40","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"Haddock: a protein- protein docking\napproach based on biochemical or biophysical information","volume":"125","author":"Dominguez","year":"2003","journal-title":"J. Am. Chem. 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Protein Chem."},{"key":"2026090307182778200_cit43","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1021\/acs.biochem.9b01055","article-title":"Overcharging\nof the zinc ion in the structure of the zinc-finger protein is needed\nfor dna binding stability","volume":"59","author":"Nguyen","year":"2020","journal-title":"Biochemistry"},{"key":"2026090307182778200_cit44","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh\newald: An n log (n)\nmethod for ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem.\nPhys."},{"key":"2026090307182778200_cit45","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"Vmd: visual\nmolecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. 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Model."},{"key":"2026090307182778200_cit50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0325830","article-title":"In silico\nanalysis of quorum sensing modulators: Insights into molecular docking\nand dynamics and potential therapeutic applications","volume":"20","author":"Alisaac","year":"2025","journal-title":"PLoS One"},{"key":"2026090307182778200_cit51","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W\nand Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c06201","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/34\/51792\/66887057\/acsomega.6c06201.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/34\/51792\/66887057\/acsomega.6c06201.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:18:35Z","timestamp":1788434315000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/34\/51792\/5277227\/Toward-an-Aptamer-Based-Biosensor-for-Cross"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":51,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,19]]},"published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c06201","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}