Virtual Screening, Selection and Molecular Dynamics of Protein Inhibitors N-myristoyltransferase (NMT) in Plasmodium vivax

Abstract

CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoTrabalho de Conclusão de Curso (Graduação)Malaria is one of several neglected diseases characterized by parasitic infection of global importance present in tropical countries. Malaria is caused by protozoa, belonging the genus Plasmodium and the vector for the transmission of the disease are female of the Anopheles mosquitoes infected with the Plasmodium ssp. According the World Health Organization (WHO), there was 219 million malaria cases worldwide in 2017, and approximately 435 000 malaria deaths in the same year. The increasing resistance to treatment has posed a major problem since the beginning of the 21st century, and with this, new research has been done with the intention of finding a new drug to be used for the eradication of the disease. A new protein has been studied as a potential target drug in malaria, N-myristoyltransferase (NMT), and the NMT acts on myristoylation of proteins, facilitating the binding of these to the plasma membrane and also contributes to the stabilization of protein-protein interactions. By inhibiting NMT it has already been established that the cell of the parasite can be killed. Therefore, in order to predict and detect potential inhibitors against Plasmodium NMT, the bioinformatic tools were used in this work, encompassing the virtual screening, docking, validation and molecular dynamics. With the analysis performed during the work it was possible to obtain compounds with great similarity to the original ligand, thus being good potential inhibitors of Plasmodium NMT