Molecular Dynamics Simulations of Cruzipains 1 and 2 at Different Temperatures

摘要

Nearly 100 years after the discovery of Trypanosoma cruzi, the parasitic agent of Chagas’ disease, there are no appropriate therapies that lead to cure the acute or the chronic phases of this disease. Among the enzymes of T. cruzi, already considered as molecular targets for Chagas’ disease treatment, the cysteine proteases had been extensively studied by experimental approaches. In the present work, the isoforms 1 and 2 of cruzipain were investigated by molecular dynamics simulations (MD) at 25°C and 37°C temperatures, using as control papain, the representative enzyme of cysteine proteases family C1. The main results showed that the presence of a negatively charged amino acid at the 158 position (papain numbering) in the catalytic site, could induces a structural reorganisation, susceptible to temperature variations, in the catalytic residues CYS25 and HIS159.