{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:05:12Z","timestamp":1789506312576,"version":"build-2803163510"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["PMDS22062928944"],"award-info":[{"award-number":["PMDS22062928944"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aptamers are versatile single-stranded nucleic acids with high specificity and stability, making them ideal for targeting challenging biomolecules. Their structural flexibility enables selective recognition of nonprotein targets such as microRNAs (miRNAs). Among these, miR-10b plays a pivotal role in cancer progression and metastasis through its oncogenic 5p and 3p arms. We propose designing aptamers specifically targeting miR-10b through a computational framework to enable precise and efficient regulation of aberrant miRNA activity in cancer. Herein, we introduce a multiscale computational workflow built on the T_SELEX framework, integrating sequence generation, folding of secondary and tertiary structure prediction, then virtual screening, quantum mechanical (QM) calculations, molecular dynamics (MD) simulations, and MM-GBSA analysis for the design and evaluation of RNA aptamer candidates targeting pre-miR-10b and its mature 5p and 3p arms. This robust workflow enables large-scale identification and structural evaluation of computationally promising RNA aptamer candidates for RNA-targeted drug discovery. In this study, a library of 1100 22-mer aptamers was virtually screened, with heatmap and interaction energy analyses revealing strong affinities toward hsa-miR-25-5p. Molecular docking identified aptamer557 as the top binder to miR-10b-3p with \u2212545.96 docking score and aptamer899 as the best for miR-10b-5p with \u2212482.55 docking score. QM single-point calculations assessed electronic stability via total molecular energy and the HOMO\u2013LUMO gaps, showing model-dependent variations. MD simulations incorporated novel stability metrics combining RMSD area integration and changepoint detection, alongside hydrogen bonding, RMSF, and radius of gyration analyses. The miR-10b-3p complexes exhibited lower RMSF and RMSD values with more persistent hydrogen bonds, reflecting stronger and more stable interactions than 5p complexes. Interestingly, despite both the aptamer and target miRNA adopting folded secondary and tertiary structures, partial Watson\u2013Crick interactions were observed during both docking and molecular dynamics simulations, particularly at accessible loop and terminal regions, suggesting a hybrid binding mechanism involving localized base pairing together with structure-dependent structural recognition. MM-GBSA binding energy analysis further supported these findings, confirming that our T-SELEX-guided in silico strategy identifies computationally promising aptamer-like candidates and provides a robust framework for the rational design of RNA-targeting therapeutics.<\/jats:p>","DOI":"10.1021\/acsomega.6c03088","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:30:59Z","timestamp":1788402659000},"page":"53904-53920","source":"Crossref","is-referenced-by-count":0,"title":["Computational Design of RNA Aptamers Targeting Oncogenic\nmiR-10b Using T-SELEX and Molecular Dynamics-Based Stability\nMetrics"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8641-0892","authenticated-orcid":true,"given":"Kabelo Phuti","family":"Mokgopa","sequence":"first","affiliation":[{"name":"Rhodes University , , ,","place":["Makhanda, South Africa, 6140"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-0790","authenticated-orcid":true,"given":"Kevin A.","family":"Lobb","sequence":"additional","affiliation":[{"name":"Rhodes University , , ,","place":["Makhanda, South Africa, 6140"]},{"name":"Rhodes University , , ,","place":["Makhanda, South Africa, 6140"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tendamudzimu","family":"Tshiwawa","sequence":"additional","affiliation":[{"name":"Rhodes University , , ,","place":["Makhanda, South Africa, 6140"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"6363","key":"2026091516123809000_cit1","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/355850a0","article-title":"Selection in vitro of single-stranded DNA molecules\nthat fold into specific ligand-binding structures","volume":"355","author":"Ellington","year":"1992","journal-title":"Nature"},{"issue":"3","key":"2026091516123809000_cit2","doi-asserted-by":"publisher","first-page":"a003582","DOI":"10.1101\/cshperspect.a003582","article-title":"Aptamers and the RNA\nworld, past and present","volume":"4","author":"Gold","year":"2012","journal-title":"Cold Spring Harbor\nPerspect. Biol."},{"key":"2026091516123809000_cit3","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.biochi.2018.09.001","article-title":"SELEX methods\non the\nroad to protein targeting with nucleic acid aptamers","volume":"154","author":"Bayat","year":"2018","journal-title":"Biochimie"},{"issue":"6","key":"2026091516123809000_cit4","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/j.biotechadv.2015.02.008","article-title":"Current approaches\nin SELEX: An update to aptamer selection technology","volume":"33","author":"Darmostuk","year":"2015","journal-title":"Biotechnol. Adv."},{"key":"2026091516123809000_cit5","doi-asserted-by":"publisher","first-page":"117831","DOI":"10.1016\/j.bmc.2024.117831","article-title":"Peptide-based\nCE-SELEX enables convenient isolation of aptamers specifically recognizing\nCD20-expressing cells","volume":"110","author":"Cossu","year":"2024","journal-title":"Bioorg. Med. Chem."},{"key":"2026091516123809000_cit6","unstructured":"Ka\u0308rkka\u0308inen, R. M.\n          \n          Production of DNA aptamers with specificity for bacterial food pathogens. Doctoral dissertation; University of Chester, 2012."},{"key":"2026091516123809000_cit7","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s00253-005-0193-5","article-title":"Aptamers basic research,\ndrug development, and clinical applications","volume":"69","author":"Proske","year":"2005","journal-title":"Appl. Microbiol. Biotechnol."},{"issue":"23","key":"2026091516123809000_cit8","doi-asserted-by":"publisher","first-page":"4377","DOI":"10.3390\/molecules24234377","article-title":"Anything you can do,\nI can do better: Can aptamers replace antibodies in clinical diagnostic\napplications?","volume":"24","author":"Bauer","year":"2019","journal-title":"Molecules"},{"issue":"1","key":"2026091516123809000_cit9","doi-asserted-by":"publisher","first-page":"107","DOI":"10.37349\/etat.2021.00035","article-title":"Aptamers and\nantibodies:\nrivals or allies in cancer targeted therapy?","volume":"2","author":"Agnello","year":"2021","journal-title":"Explor. Targeted Anti-Tumor Ther."},{"key":"2026091516123809000_cit10","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.bios.2014.09.026","article-title":"Aptamers\nas a replacement\nfor antibodies in enzyme-linked immunosorbent assay","volume":"64","author":"Toh","year":"2015","journal-title":"Biosens. Bioelectron."},{"issue":"13","key":"2026091516123809000_cit11","first-page":"5227","article-title":"Efficacy\nand Safety of Maintenance Therapy With Pegaptanib Sodium in Neovascular\nAMD (NV-AMD)-1-Year Results of the LEVEL Study","volume":"50","author":"Weber","year":"2009","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"2026091516123809000_cit12","doi-asserted-by":"crossref","DOI":"10.5772\/22350","article-title":"Advances in aptamer-based\nbiosensors for food safety","volume-title":"Environmental\nBiosensors","author":"McKeague","year":"2011"},{"issue":"4","key":"2026091516123809000_cit13","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.ophtha.2006.01.027","article-title":"Tolerability and efficacy\nof multiple escalating doses of ranibizumab (Lucentis) for neovascular\nage-related macular degeneration","volume":"113","author":"Rosenfeld","year":"2006","journal-title":"Ophthalmology"},{"issue":"4","key":"2026091516123809000_cit14","first-page":"309","article-title":"Multi-step cascade\nof tumor cell metastasis","volume":"6","author":"Stracke","year":"1992","journal-title":"In Vivo"},{"issue":"8","key":"2026091516123809000_cit15","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.1093\/nar\/gki567","article-title":"Clustering\nand conservation patterns of human microRNAs","volume":"33","author":"Altuvia","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2026091516123809000_cit16","doi-asserted-by":"crossref","unstructured":"Mokgopa, K. P.; Alan Lobb, K.; Tshiwawa, T.\n          T_SELEX program:\nTheoretical SELEX tool for Rational Design and Selection of RNA Aptamers\nTargeting Macromolecules, 2024.","DOI":"10.21203\/rs.3.rs-5038044\/v1"},{"issue":"3","key":"2026091516123809000_cit17","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3390\/biotech14030072","article-title":"Benchmarking the Base\nRandomization Algorithm as a Possible Tool for the Initial Step of\nGenerating a Virtual RNA Aptamers Library","volume":"14","author":"Mokgopa","year":"2025","journal-title":"BioTech"},{"key":"2026091516123809000_cit18","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1748-7188-6-26","article-title":"ViennaRNA\nPackage 2.0","volume":"6","author":"Lorenz","year":"2011","journal-title":"Algorithms Mol. 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Sci."},{"issue":"12","key":"2026091516123809000_cit22","doi-asserted-by":"publisher","first-page":"3831","DOI":"10.3390\/cancers12123831","article-title":"Premature MicroRNA-based therapeutic: A \u201cone-two punch\u201d\nagainst cancers","volume":"12","author":"Chen","year":"2020","journal-title":"Cancers"},{"key":"2026091516123809000_cit23","doi-asserted-by":"publisher","first-page":"e257","DOI":"10.1016\/j.fsigss.2017.09.092","article-title":"Expression difference\nof miR-10b and miR-135b between the fertile and infertile semen samples\n(p)","volume":"6","author":"Tian","year":"2017","journal-title":"Forensic Sci. Int. Genet. Suppl. Ser."},{"issue":"11","key":"2026091516123809000_cit24","doi-asserted-by":"publisher","first-page":"7986","DOI":"10.1074\/jbc.m109.062877","article-title":"MicroRNA-10b promotes\nmigration and invasion through KLF4 in human\nesophageal cancer cell lines","volume":"285","author":"Tian","year":"2010","journal-title":"J. Biol. 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Chem. Theory Comput."},{"issue":"16","key":"2026091516123809000_cit36","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: fast, flexible, and free","volume":"26","author":"Van Der Spoel","year":"2005","journal-title":"J. Comput. Chem."},{"issue":"9","key":"2026091516123809000_cit37","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development\nand testing of a general amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"issue":"4","key":"2026091516123809000_cit38","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1021\/acs.jctc.7b00028","article-title":"How molecular size impacts RMSD applications\nin molecular dynamics simulations","volume":"13","author":"Sargsyan","year":"2017","journal-title":"J. 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Stat."},{"key":"2026091516123809000_cit42","first-page":"1047","article-title":"Fuzzification\nof Simpson\u2019s 1\/3 Rule and Development of its Computer 243 Program","volume":"11","author":"Bora","year":"2023","journal-title":"J. Coastal Life Med."},{"issue":"10","key":"2026091516123809000_cit43","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.3390\/sym13101933","article-title":"On weighted\nSimpson\u2019s 3 8 rule","volume":"13","author":"Rostamian Delavar","year":"2021","journal-title":"Symmetry"},{"issue":"11","key":"2026091516123809000_cit44","doi-asserted-by":"publisher","first-page":"132","DOI":"10.26782\/jmcms.2020.11.00012","article-title":"A New and Efficient\nSimpson\u2019s 1\/3-Type Quadrature Rule For Riemann-Stieltjes Integral","volume":"15","author":"Memon","year":"2020","journal-title":"J. Mech. Contin. Math. Sci."},{"issue":"W1","key":"2026091516123809000_cit45","doi-asserted-by":"publisher","first-page":"W435","DOI":"10.1093\/nar\/gkx279","article-title":"IntaRNA 2.0: enhanced\nand customizable\nprediction of RNA\u2013RNA interactions","volume":"45","author":"Mann","year":"2017","journal-title":"Nucleic\nAcids Res."},{"key":"2026091516123809000_cit46","unstructured":"BIOVIA, Dassault Syste\u0300mes.\n          \n          Discovery Studio Visualizer, v21.1.0.20298; Dassault Syste\u0300mes: San Diego, 2021."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c03088","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/36\/53904\/67983097\/acsomega.6c03088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/36\/53904\/67983097\/acsomega.6c03088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:12:53Z","timestamp":1789503173000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/36\/53904\/5383434\/Computational-Design-of-RNA-Aptamers-Targeting"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":46,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,8,31]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c03088","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]}}}