{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:32:26Z","timestamp":1783744346486,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Tumor necrosis factor-\u03b1 (TNF-\u03b1) is a drug target in rheumatoid arthritis and several other auto-immune disorders. TNF-\u03b1 binds with TNF receptors (TNFR), located on the surface of several immunological cells to exert its effect. Hence, the use of inhibitors that can hinder the complex formation of TNF-\u03b1\/TNFR can be of medicinal significance. In this study, multiple chem-informatics approaches, including descriptor-based screening, 2D-similarity searching, and pharmacophore modelling were applied to screen new TNF-\u03b1 inhibitors. Subsequently, multiple-docking protocols were used, and four-fold post-docking results were analyzed by consensus approach. After structure-based virtual screening, seventeen compounds were mutually ranked in top-ranked position by all the docking programs. Those identified hits target TNF-\u03b1 dimer and effectively block TNF-\u03b1\/TNFR interface. The predicted pharmacokinetics and physiological properties of the selected hits revealed that, out of seventeen, seven compounds (4, 5, 10, 11, 13\u201315) possessed excellent ADMET profile. These seven compounds plus three more molecules (7, 8 and 9) were chosen for molecular dynamics simulation studies to probe into ligand-induced structural and dynamic behavior of TNF-\u03b1, followed by ligand-TNF-\u03b1 binding free energy calculation using MM-PBSA. The MM-PBSA calculations revealed that compounds 4, 5, 7 and 9 possess highest affinity for TNF-\u03b1; 8, 11, 13\u201315 exhibited moderate affinities, while compound 10 showed weaker binding affinity with TNF-\u03b1. This study provides valuable insights to design more potent and selective inhibitors of TNF-\u03b1, that will help to treat inflammatory disorders.<\/jats:p>","DOI":"10.3390\/biom11020329","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T14:23:27Z","timestamp":1614003807000},"page":"329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Structure-Based Virtual Screening of Tumor Necrosis Factor-\u03b1 Inhibitors by Cheminformatics Approaches and Bio-Molecular Simulation"],"prefix":"10.3390","volume":"11","author":[{"given":"Sobia Ahsan","family":"Halim","sequence":"first","affiliation":[{"name":"Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al-Mouz, Nizwa 616, Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almas Gul","family":"Sikandari","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shahzad, Islamabad 45600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajmal","family":"Khan","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al-Mouz, Nizwa 616, Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Wadood","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Qaiser","family":"Fatmi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shahzad, Islamabad 45600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7911-290X","authenticated-orcid":false,"given":"Ren\u00e9","family":"Csuk","sequence":"additional","affiliation":[{"name":"Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-5942","authenticated-orcid":false,"given":"Ahmed","family":"Al-Harrasi","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al-Mouz, Nizwa 616, Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/0022-4804(91)90146-D","article-title":"Tumor necrosis factor-\u03b1","volume":"51","author":"Rock","year":"1991","journal-title":"J. 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