Molecular Dynamics Simulations of Substrate Release from Trypanosoma cruzi UDP-Galactopyranose Mutase.
Rodrigo Cossio-PérezGustavo Pierdominici-SottileKendra BufkinJuliana PalmaPublished in: Journal of chemical information and modeling (2019)
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.
Keyphrases
- trypanosoma cruzi
- molecular dynamics simulations
- molecular dynamics
- molecular docking
- single molecule
- structural basis
- monte carlo
- amino acid
- transcription factor
- magnetic resonance imaging
- single cell
- emergency department
- healthcare
- drug induced
- magnetic resonance
- risk assessment
- human health
- combination therapy
- meta analyses
- contrast enhanced