{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T10:05:49Z","timestamp":1767261949807,"version":"3.40.5"},"reference-count":33,"publisher":"Bentham Science Publishers Ltd.","issue":"5","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CAD"],"published-print":{"date-parts":[[2020,11,9]]},"abstract":"<jats:sec>\n<jats:title>Background:<\/jats:title>\n<jats:p>Human African trypanosomiasis is a fatal disease prevalent in approximately\n36 sub-Saharan countries. Emerging reports of drug resistance in Trypanosoma brucei are a serious\ncause of concern as only limited drugs are available for the treatment of the disease. Pteridine reductase\nis an enzyme of Trypanosoma brucei.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>It plays a critical role in the pterin metabolic pathway that is absolutely essential for its survival\nin the human host. The success of finding a potent inhibitor in structure-based drug design lies\nwithin the ability of computational tools to efficiently and accurately dock a ligand into the binding\ncavity of the target protein. Here we report the computational characterization of Trypanosoma brucei\npteridine reductase (Tb-PR) active-site using twenty-four high-resolution co-crystal structures with various\ndrugs. Structurally, the Tb-PR active site can be grouped in two clusters; one with high Root Mean\nSquare Deviation (RMSD) of atomic positions and another with low RMSD of atomic positions. These\nclusters provide fresh insight for rational drug design against Tb-PR. Henceforth, the effect of several\nfactors on docking accuracy, including ligand and protein flexibility were analyzed using Fred.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>The online server was used to analyze the side chain flexibility and four proteins were selected\non the basis of results. The proteins were subjected to small-scale virtual screening using 85 compounds,\nand statistics were calculated using Bedroc and roc curves. The enrichment factor was also calculated\nfor the proteins and scoring functions. The best scoring function was used to understand the ligand\nprotein interactions with top common compounds of four proteins. In addition, we made a 3D\nstructural comparison between the active site of Tb-PR and Leishmania major pteridine reductase (Lm-\nPR). We described key structural differences between Tb-PR and Lm-PR that can be exploited for rational\ndrug design against these two human parasites.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p> The results indicated that relying just on re-docking and cross-docking experiments for\nvirtual screening of libraries isn\u2019t enough and results might be misleading. Hence it has been suggested\nthat small scale virtual screening should be performed prior to large scale screening.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1573409915666190827163327","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T14:49:20Z","timestamp":1566917360000},"page":"583-598","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of the Trypanosoma brucei Pteridine Reductase Active- Site using Computational Docking and Virtual Screening Techniques"],"prefix":"10.2174","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4690-8984","authenticated-orcid":true,"given":"Hina","family":"Shamshad","sequence":"first","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, University of Karachi, Karachi-75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9967-9564","authenticated-orcid":true,"given":"Abdul","family":"Hafiz","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9343-2595","authenticated-orcid":true,"given":"Ismail I.","family":"Althagafi","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-6375","authenticated-orcid":true,"given":"Maria","family":"Saeed","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi- 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2688-8215","authenticated-orcid":true,"given":"Agha Zeeshan","family":"Mirza","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"10429","DOI":"10.1074\/jbc.M110.209593","volume":"286","author":"Ong H.B.","year":"2011","unstructured":"Ong H.B.; Sienkiewicz N.; Wyllie S.; Fairlamb A.H.; Dissecting the metabolic roles of pteridine reductase 1 in Trypanosoma brucei and Leishmania major. 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