info:eu-repo/semantics/article
Molecular Dynamics Simulations of Substrate Release from Trypanosoma cruzi UDP-Galactopyranose Mutase
Fecha
2019-02Registro en:
Cossio Pérez, Rodrigo; Pierdominici Sottile, Gustavo; Sobrado, Pablo; Palma, Juliana Isabel; Molecular Dynamics Simulations of Substrate Release from Trypanosoma cruzi UDP-Galactopyranose Mutase; American Chemical Society; Journal of Chemical Information and Modeling; 59; 2; 2-2019; 809-817
1549-9596
CONICET Digital
CONICET
Autor
Cossio Pérez, Rodrigo
Pierdominici Sottile, Gustavo
Sobrado, Pablo
Palma, Juliana Isabel
Resumen
The enzyme UDP-galactopyranose mutase (UGM) represents a promising drug target for the treatment of infections with Trypanosoma cruzi. We have computed the Potential of Mean Force for the release of UDP-galactopyranose from UGM, using Umbrella Sampling simulations. The simulations revealed the conformational changes that both substrate and enzyme undergo during the process. It was determined that the galactopyranose portion of the substrate is highly mobile and that the opening/closing of the active site occurs in stages. Previously uncharacterized interactions with highly conserved residues were also identified. These findings provide new pieces of information that contribute to the rational design of drugs against T. cruzi.