Abstract
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.
Recommended Citation
R. Cossio-Pérez et al., "Molecular Dynamics Simulations of Substrate Release from Trypanosoma Cruzi UDP-Galactopyranose Mutase," Journal of Chemical Information and Modeling, vol. 59, no. 2, pp. 809 - 817, American Chemical Society, Feb 2019.
The definitive version is available at https://doi.org/10.1021/acs.jcim.8b00675
Department(s)
Chemistry
International Standard Serial Number (ISSN)
1549-960X; 1549-9596
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2024 American Chemical Society, All rights reserved.
Publication Date
25 Feb 2019
PubMed ID
30608160
Comments
National Science Foundation, Grant CHE-1506206