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Identifying structural similarities in proteins offers valuable insights into their function and activation mechanisms, aiding in predicting protein\u2013ligand interactions, anticipating off-target effects, and facilitating the development of therapeutic agents. Numerous computational methods assessing global or local similarity in protein cavities have emerged, but their utilization is impeded by complexity, impractical automation for amino acid pattern searches, and an inability to evaluate the dynamics of scrutinized protein\u2013ligand systems. Here, we present a general, automatic and unbiased computational pipeline, named\n                    <jats:italic>VirtuousPocketome<\/jats:italic>\n                    , aimed at screening huge databases of proteins for similar binding pockets starting from an interested protein\u2013ligand complex. We demonstrate the pipeline's potential by exploring a recently-solved human bitter taste receptor, i.e. the TAS2R46, complexed with strychnine. We pinpointed 145 proteins sharing similar binding sites compared to the analysed bitter taste receptor and the enrichment analysis highlighted the related biological processes, molecular functions and cellular components. This work represents the foundation for future studies aimed at understanding the effective role of tastants outside the gustatory system: this could pave the way towards the rationalization of the diet as a supplement to standard pharmacological treatments and the design of novel tastants-inspired compounds to target other proteins involved in specific diseases or disorders. The proposed pipeline is publicly accessible, can be applied to any protein\u2013ligand complex, and could be expanded to screen any database of protein structures.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-56893-7","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T09:01:44Z","timestamp":1710493304000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["VirtuousPocketome: a computational tool for screening protein\u2013ligand complexes to identify similar binding sites"],"prefix":"10.1038","volume":"14","author":[{"given":"Lorenzo","family":"Pallante","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cannariato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lampros","family":"Androutsos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Zizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agorakis","family":"Bompotas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xhesika","family":"Hada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianvito","family":"Grasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Kalogeras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seferina","family":"Mavroudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Di Benedetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Theofilatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Deriu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"56893_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/40310","volume":"388","author":"PJ Artymiuk","year":"1997","unstructured":"Artymiuk, P. 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