Molecular Modeling applied in the Structural Analysis and Comparison of Sirtuin 2 enzymes from Trypanosomatids

Leishmaniasis is a neglected disease that affects a large part of the world's population and cause severe socioeconomic impacts. The drugs available for its treatment are inefficient and present serious adverse effects. Sirtuin 2 is an epigenetic enzyme essential for the survival of Trypanosomatid parasites. Since only one Trypanosomatid Sirtuin structure is available, to study this biochemical target we performed the Homology Modeling of four species of parasites. Molecular Dynamic Simulations were conducted in the GROMACS package to refine the constructed models and to evaluate the stability of different protein-ligand complexes obtained through superposition with co-crystals and Molecular Docking. The validated models of the different complexes were compared with the human structure. This study provides us a theoretical basis for the search for novel Sirtuin 2 ligands more selective and potent against the parasitic enzyme, thus paving the way for the development of safer and more effective leishmanicidal drug candidates.