Toxoplasma gondii (T. gondii)
is one of the most successful parasites in the world, because about a
third of the worlds population is seropositive for toxoplasmosis.
Treatment regimens for toxoplasmosis have remained unchanged for the
past 20 years, and no new drugs have been introduced to the market
recently. This study, performed molecular docking to identify
interactions of FDA-approved drugs with essential residues in the active
site of proteins of T. gondii Dihydrofolate Reductase (TgDHFR),
Prolyl-tRNA Synthetase (TgPRS), and Calcium-Dependent Protein Kinase 1
(TgCDPK1). Each protein was docked with 2100 FDA-approved drugs using
AutoDock Vina. Also, the Pharmit software was used to generate
pharmacophore models based on the TgDHFR complexed with TRC-2533, TgPRS
in complex with halofuginone, and TgCDPK1 in complex with a bumped
kinase inhibitor, RM-1–132. Molecular dynamics (MD) simulation was also
performed for 100 ns to verify the stability of interaction in
drug–protein complexes. Molecular Mechanics Poisson-Boltzmann Surface
Area (MMPBSA) analysis evaluated the binding energy of selected
complexes. Ezetimibe, Raloxifene, Sulfasalazine, Triamterene, and
Zafirlukast drugs against the TgDHFR protein, Cromolyn, Cefexim, and
Lactulose drugs against the TgPRS protein, and Pentaprazole,
Betamethasone, and Bromocriptine drugs against TgCDPK1 protein showed
the best results. These drugs had the lowest energy-based docking scores
and also stable interactions based on MD analyses with TgDHFR, TgPRS,
and TgCDPK1 drug targets that can be introduced as possible drugs for
laboratory investigations to treat T. gondii parasite infection.