{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:31:17Z","timestamp":1768887077445,"version":"3.49.0"},"reference-count":79,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04378\/2020, UIDB\/04378\/2020, IF\/00052\/2014, UID\/QUI\/50006\/2019, and 2020.01423.CEECIND"],"award-info":[{"award-number":["UIDP\/04378\/2020, UIDB\/04378\/2020, IF\/00052\/2014, UID\/QUI\/50006\/2019, and 2020.01423.CEECIND"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Biofilms are aggregates of microorganisms anchored to a surface and embedded in a self-produced matrix of extracellular polymeric substances and have been associated with 80% of all bacterial infections in humans. Because bacteria in biofilms are less amenable to antibiotic treatment, biofilms have been associated with developing antibiotic resistance, a problem that urges developing new therapeutic options and approaches. Interfering with quorum-sensing (QS), an important process of cell-to-cell communication by bacteria in biofilms is a promising strategy to inhibit biofilm formation and development. Here we describe and apply an in silico computational protocol for identifying novel potential inhibitors of quorum-sensing, using CviR\u2014the quorum-sensing receptor from Chromobacterium violaceum\u2014as a model target. This in silico approach combines protein-ligand docking (with 7 different docking programs\/scoring functions), receptor-based virtual screening, molecular dynamic simulations, and free energy calculations. Particular emphasis was dedicated to optimizing the discrimination ability between active\/inactive molecules in virtual screening tests using a target-specific training set. Overall, the optimized protocol was used to evaluate 66,461 molecules, including those on the ZINC\/FDA-Approved database and to the Mu.Ta.Lig Virtual Chemotheca. Multiple promising compounds were identified, yielding good prospects for future experimental validation and for drug repurposing towards QS inhibition.<\/jats:p>","DOI":"10.3390\/molecules26092600","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T10:30:41Z","timestamp":1619692241000},"page":"2600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Identification of New Potential Inhibitors of Quorum Sensing through a Specialized Multi-Level Computational Approach"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6257-8885","authenticated-orcid":false,"given":"F\u00e1bio G.","family":"Martins","sequence":"first","affiliation":[{"name":"UCIBIO\/REQUIMTE, BioSIM\u2014Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias da Universidade do Porto, 4169-007 Porto, Portugal"}]},{"given":"Andr\u00e9","family":"Melo","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias da Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-5284","authenticated-orcid":false,"given":"S\u00e9rgio F.","family":"Sousa","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, BioSIM\u2014Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1351\/PAC-REC-10-12-04","article-title":"Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)","volume":"84","author":"Vert","year":"2012","journal-title":"Pure Appl. 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