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Traditional pocket-based predictors miss $\\sim $18% of experimentally confirmed sites that lie outside surface invaginations. To overcome this limitation, we developed STINGAllo, an interactive web server that introduces a residue-centric machine-learning model. Using 54 optimized internal protein nanoenvironment descriptors, STINGAllo predicts allosteric site-forming residues at single-residue resolution. By integrating hydrophobic interaction networks, local density, graph connectivity, and a unique \u201csponge effect\u201d metric, STINGAllo detects allosteric sites independently of surface geometry, including concave pockets, flat surfaces, or even cryptic regions. It achieves a success rate of $\\sim $78% on benchmark datasets, substantially outperforming existing methods with a 60.2% overall success rate compared with 21.1%\u201324.2% for contemporary pocket-based predictors. Our analysis further reveals that nearly 52.7% of unique proteins in the Protein Data Bank [(PDB); 119 851 entries, 14 November 2024] contain at least one chain with a predicted allosteric site. STINGAllo accepts protein structures via PDB identifiers or custom uploads, provides interactive 3D visualization of predicted pockets, and supports integration into computational pipelines through a RESTful application programming interface. Overall, STINGAllo bridges advanced computational prediction with user-friendly design, offering a robust tool expected to deepen understanding of protein regulation and accelerate allosteric drug discovery. The server is freely accessible at https:\/\/www.stingallo.cbi.cnptia.embrapa.br\/.<\/jats:p>","DOI":"10.1093\/bib\/bbaf424","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T12:20:17Z","timestamp":1755778817000},"source":"Crossref","is-referenced-by-count":5,"title":["STINGAllo: a web server for high-throughput prediction of allosteric site-forming residues using internal protein nanoenvironment descriptors"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-5034","authenticated-orcid":false,"given":"Folorunsho Bright","family":"Omage","sequence":"first","affiliation":[{"name":"Computational Biology Research Group, Embrapa Digital Agriculture , Av. 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Andr\u00e9 Tosello, 209, Bar\u00e3o Geraldo, Campinas, SP, CEP 13083-886 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2698-6309","authenticated-orcid":false,"given":"In\u00e1cio Henrique","family":"Yano","sequence":"additional","affiliation":[{"name":"Computational Biology Research Group, Embrapa Digital Agriculture , Av. Andr\u00e9 Tosello, 209, Bar\u00e3o Geraldo, Campinas, SP, CEP 13083-886 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-8677","authenticated-orcid":false,"given":"Jorge Enrique","family":"Hern\u00e1ndez Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Multiuser Center for Biomolecular Innovation, Institute of Biosciences, Humanities and Exact Sciences, S\u00e3o Paulo State University (UNESP) , Rua Crist\u00f3v\u00e3o Colombo, 2265, Jardim Nazareth, S\u00e3o Jos\u00e9 do Rio Preto, SP, CEP 15054-000 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9991-6566","authenticated-orcid":false,"given":"Poliana Fernanda","family":"Giachetto","sequence":"additional","affiliation":[{"name":"Computational Biology Research Group, Embrapa Digital Agriculture , Av. Andr\u00e9 Tosello, 209, Bar\u00e3o Geraldo, Campinas, SP, CEP 13083-886 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-7332","authenticated-orcid":false,"given":"Ljubica","family":"Tasic","sequence":"additional","affiliation":[{"name":"Biological Chemistry Laboratory , Department of Organic Chemistry, Institute of Chemistry, , Rua Josu\u00e9 de Castro, s\/n \u2013 Cidade Universit\u00e1ria \u201cZeferino Vaz\u201d, Bar\u00e3o Geraldo, Campinas, SP, CEP 13083-861 ,","place":["Brazil"]},{"name":"University of Campinas (UNICAMP) , Department of Organic Chemistry, Institute of Chemistry, , Rua Josu\u00e9 de Castro, s\/n \u2013 Cidade Universit\u00e1ria \u201cZeferino Vaz\u201d, Bar\u00e3o Geraldo, Campinas, SP, CEP 13083-861 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-1145","authenticated-orcid":false,"given":"Raghuvir Krishnaswamy","family":"Arni","sequence":"additional","affiliation":[{"name":"Multiuser Center for Biomolecular Innovation, Institute of Biosciences, Humanities and Exact Sciences, S\u00e3o Paulo State University (UNESP) , Rua Crist\u00f3v\u00e3o Colombo, 2265, Jardim Nazareth, S\u00e3o Jos\u00e9 do Rio Preto, SP, CEP 15054-000 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4982-0416","authenticated-orcid":false,"given":"Goran","family":"Neshich","sequence":"additional","affiliation":[{"name":"Computational Biology Research Group, Embrapa Digital Agriculture , Av. 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