{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T09:34:01Z","timestamp":1769765641656,"version":"3.49.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T00:00:00Z","timestamp":1360281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The aim of this work was to solve the structure of the enzyme dihydrofolate reductase from Toxoplasma gondii (TgondiiDHFR) as a target for drug discovery on account of recent reports of parasite's growing resistance to pyrimethamine (CP6), which is the reference pharmaceutical used to treat toxoplasmosis and malaria. The tertiary structure of the protein bonded to NADP+ and CP6 was solved by homology modeling. The best output model was subjected to conjugate gradient minimization and the comparison with templates shows important replacements at the inhibitor's binding site allowing selective drug design. CP6 redocking in TgondiiDHFR shows a \u0394Gbinding of \u22128.66 kcal mol\u22121, higher than those found for templates Plasmodium vivax (\u22129.01) and P. falciparum (\u22128.99). Virtual screening of ligands similar to CP6 was performed using the ZINC database and docking procedures were carried out. The result indicates the substances ZINC14966516, ZINC13685962, ZINC13685929 and ZINC13686062 with a \u0394Gbinding of \u221210.57, \u221210.09, \u22129.87, and \u22129.76 kcal mol\u22121, respectively, as the best choices. NPT molecular dynamics with the complexes indicates that they remained stable along the 10 ns simulation and they dock to TgondiiDHFR by salt bridges to the Asp 30 and to nine other residues in the contact region, which makes it more difficult for single mutations to acquire resistance. The contact frequency of protein residues with ligands suggests plausible explanations for site-directed mutagenesis studies regarding CP6 resistance described previously in the literature. All results indicate that the new ligands could be tested as pyrimethamine substitutes in the treatment of toxoplasmosis, in addition to other protozoonosis diseases.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/c3mb25530a","type":"journal-article","created":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T06:31:13Z","timestamp":1360305073000},"page":"1308-1315","source":"Crossref","is-referenced-by-count":12,"title":["Homology modeling of dihydrofolate reductase from\n                    <i>T. gondii<\/i>\n                    bonded to antagonists: molecular docking and molecular dynamics simulations"],"prefix":"10.1093","volume":"9","author":[{"given":"D\u00e9bora","family":"Pacheco Homem","sequence":"first","affiliation":[{"name":"State University of Maring\u00e1 a , Av. Colombo 5790, Maring\u00e1, PR, Brazil \u00a0 favseixas@uem.br \u00a0 +55 44 36219326 \u00a0 +55 44 36219300"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Rog\u00e9rio","family":"Flores","sequence":"additional","affiliation":[{"name":"State University of Maring\u00e1 a , Av. Colombo 5790, Maring\u00e1, PR, Brazil \u00a0 favseixas@uem.br \u00a0 +55 44 36219326 \u00a0 +55 44 36219300"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla","family":"Tosqui","sequence":"additional","affiliation":[{"name":"Regional College of Technology b , Av. Francisco das Chagas Oliveira 791, S\u00e3o Jos\u00e9 do Rio Preto, SP, Brazil \u00a0 +55 17 33646598 \u00a0 +55 17 33646589"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago","family":"de Castro Rozada","sequence":"additional","affiliation":[{"name":"State University of Maring\u00e1 a , Av. Colombo 5790, Maring\u00e1, PR, Brazil \u00a0 favseixas@uem.br \u00a0 +55 44 36219326 \u00a0 +55 44 36219300"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernani","family":"Abicht Basso","sequence":"additional","affiliation":[{"name":"State University of Maring\u00e1 a , Av. Colombo 5790, Maring\u00e1, PR, Brazil \u00a0 favseixas@uem.br \u00a0 +55 44 36219326 \u00a0 +55 44 36219300"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arquimedes","family":"Gasparotto Junior","sequence":"additional","affiliation":[{"name":"Paranaense University, P\u00e7a. Mascarenhas de Moraes c , 4282, Umuarama, PR, Brazil \u00a0 gasparotto@unipar.br \u00a0 +55 44 3621-2830 \u00a0 +55 44 3621-2830"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Augusto Vicente Seixas","sequence":"additional","affiliation":[{"name":"State University of Maring\u00e1 a , Av. Colombo 5790, Maring\u00e1, PR, Brazil \u00a0 favseixas@uem.br \u00a0 +55 44 36219326 \u00a0 +55 44 36219300"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,2,8]]},"reference":[{"key":"2026012913100185100_cit1","doi-asserted-by":"crossref","DOI":"10.1002\/9783527633883","volume-title":"Apicomplexan parasites: Molecular Approaches toward Targeted Drug Development","author":"Becker","year":"2011"},{"key":"2026012913100185100_cit2","author":"CDC, Centers for Disease Control and Prevention, 2012"},{"key":"2026012913100185100_cit3","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1590\/S0100-72032004000800006","volume":"26","author":"Le\u00e3o","year":"2004","journal-title":"Rev. Bras. Ginecol. Obstet."},{"key":"2026012913100185100_cit4","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1146\/annurev.mi.49.100195.002235","volume":"49","author":"Borst","year":"1995","journal-title":"Annu. Rev. 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