Insights into the structure and inhibition of <i>Giardia intestinalis</i> arginine deiminase: homology modeling, docking, and molecular dynamics studies

<p><i>Giardia intestinalis</i> arginine deiminase (<i>GiADI</i>) is an important metabolic enzyme involved in the energy production and defense of this protozoan parasite. The lack of this enzyme in the human host makes <i>GiADI</i> an attractive target for drug design against <i>G. intestinalis</i>. One approach in the design of inhibitors of <i>GiADI</i> could be computer-assisted studies of its crystal structure, such as docking; however, the required crystallographic structure of the enzyme still remains unresolved. Because of its relevance, in this work, we present a three-dimensional structure of <i>GiADI</i> obtained from its amino acid sequence using the homology modeling approximation. Furthermore, we present an approximation of the most stable dimeric structure of <i>GiADI</i> identified through molecular dynamics simulation studies. An <i>in silico</i> analysis of druggability using the structure of <i>GiADI</i> was carried out in order to know if it is a good target for design and optimization of selective inhibitors. Potential <i>GiADI</i> inhibitors were identified by docking of a set of 3196 commercial and 19 <i>in</i>-<i>house</i> benzimidazole derivatives, and molecular dynamics simulation studies were used to evaluate the stability of the ligand–enzyme complexes.</p