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Biofilm formation, a critical characteristic of S. mutans, is regulated by quorum sensing (QS). This study aimed to utilize pharmacoinformatics techniques to screen and identify effective phytochemicals that can target specific proteins involved in the quorum sensing pathway of S. mutans. A computational approach involving homology modeling, model validation, molecular docking, and molecular dynamics (MD) simulation was employed. The 3D structures of the quorum sensing target proteins, namely SecA, SMU1784c, OppC, YidC2, CiaR, SpaR, and LepC, were modeled using SWISS-MODEL and validated using a Ramachandran plot. Metabolites from Azadirachta indica (Neem), Morinda citrifolia (Noni), and Salvadora persica (Miswak) were docked against these proteins using AutoDockTools. MD simulations were conducted to assess stable interactions between the highest-scoring ligands and the target proteins. Additionally, the ADMET properties of the ligands were evaluated using SwissADME and pkCSM tools. The results demonstrated that campesterol, meliantrol, stigmasterol, isofucosterol, and ursolic acid exhibited the strongest binding affinity for CiaR, LepC, OppC, SpaR, and Yidc2, respectively. Furthermore, citrostadienol showed the highest binding affinity for both SMU1784c and SecA. Notably, specific amino acid residues, including ASP86, ARG182, ILE179, GLU143, ASP237, PRO101, and VAL84 from CiaR, LepC, OppC, SecA, SMU1784c, SpaR, and YidC2, respectively, exhibited significant interactions with their respective ligands. While the docking study indicated favorable binding energies, the MD simulations and ADMET studies underscored the substantial binding affinity and stability of the ligands with the target proteins. However, further in vitro studies are necessary to validate the efficacy of these top hits against S. mutans.<\/jats:p>","DOI":"10.3390\/molecules28145514","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T21:22:58Z","timestamp":1689801778000},"page":"5514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacoinformatics-Based Approach for Uncovering the Quorum-Quenching Activity of Phytocompounds against the Oral Pathogen, Streptococcus mutans"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-2792","authenticated-orcid":false,"given":"Shakti Chandra Vadhana","family":"Marimuthu","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayaprabhakaran","family":"Murugesan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2398-8448","authenticated-orcid":false,"given":"Ewa","family":"Babkiewicz","sequence":"additional","affiliation":[{"name":"Department of Hydrobiology, Faculty of Biology, University of Warsaw, 02-089 Warsaw, Poland"},{"name":"Biological and Chemical Research Centre, University of Warsaw, 02-089 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Maszczyk","sequence":"additional","affiliation":[{"name":"Department of Hydrobiology, Faculty of Biology, University of Warsaw, 02-089 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3680-1577","authenticated-orcid":false,"given":"Murugesan","family":"Sankaranarayanan","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Pilani 333031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1546-6279","authenticated-orcid":false,"given":"Esakkimuthu","family":"Thangamariappan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph Christina","family":"Rosy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8458-4546","authenticated-orcid":false,"given":"Sureshbabu","family":"Ram Kumar Pandian","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-5118","authenticated-orcid":false,"given":"Selvaraj","family":"Kunjiappan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5687-0588","authenticated-orcid":false,"given":"Vanavil","family":"Balakrishnan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7156-1057","authenticated-orcid":false,"given":"Krishnan","family":"Sundar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1128\/mr.50.4.353-380.1986","article-title":"Role of Streptococcus mutans in human dental decay","volume":"50","author":"Loesche","year":"1986","journal-title":"Microbiol. 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