In silico molecular modeling and docking studies on the Leishmania mitochondrial iron transporter-1 (LMIT1)

Leishmania mitochondrial iron transporter-1 (LMIT1) is a transmembrane protein required for normal mitochondrial structure and function. This protein is essential for the replication, survival, virulence, and the differentiation of promastigotes into infective amastigotes. Regarding the important role of LMIT1 in the iron-regulated process in Leishmania parasites, it can be considered as a promising target for structure-based drug design against leishmaniasis. In the present study, the three-dimensional (3D) structure of LMIT1 was determined by various in silico modeling approaches. The quality of the built models was evaluated using the different servers. The best model, which was predicted by Robetta, was selected for following analyses. Thereafter, the obtained model was successfully refined and used for determination of its probable inhibitors. Virtual screening of an approved compound library was employed to find the probable LMIT1 inhibitors. Ultimately, six molecules were found to inhibit the iron interaction with the LMIT1 in proper orientation and binding energy. The inhibitor candidates are shown to interact with functional residues of LMIT1. The achieved compounds could pave the way toward the development of new drugs against leishmaniasis in future studies.