Akademik Veri Yönetim Sistemi
AFRICAN JOURNAL OF MICROBIOLOGY RESEARCH, cilt.6, sa.5, ss.917-926, 2012 (SCI-Expanded)
This research aimed to generate and validate the three-dimensional structure of mostly targeted proteins of leishmania using homology modeling tools and then virtual screening and docking the available chemical and medicinal plants compounds to the generated proteins as the receptor. Overall, 12 drugs and 10 medicinal plants compounds were selected for internal and comparative study. Then 18 experimental ligands were docked using AutoDock 4.3 program into the active sites of leishmania donovani pteridine reductase 1, which was modeled using homology modeling programs. Out of 28 templates, the best one (PDB ID: 1W0cA) showed 97.17% sequence identity, E-value of 9.13483e-147 and final total model energy of -12574.484 kJ/mol. Validation of different models of pteridine reductase 1 (PTR1) was carried out and ramachandran plot was computed, which showed 96.75% residues in favored and allowed regions. Furthermore, ERRAT program observed the overall quality factor of the prepared model as 92.937. Vinblastine and diospyrin in the medicinal plants group showed the highest biding affinity. Compounds 11 and 3 are more active on leishmania PTR1 with IC50 of 25 and 35 mu M, respectively. The hope of identifying novel drug targets and vaccine candidates against parasitic protozoan is laying on their peptides, currently. The homology or comparative modeling due to its simplicity to predict the structure of the target proteins or peptides with the help of available protein structure as temples has come as a rescue. Thus, it could be concluded that our generated experimental drug compounds could have potential as pharmacological tools against the visceral leishmaniasis.