Mixed quantum/classical studies of Trypanosoma cruzi's trans-sialidase

CHED 1006

Jason M. Swails, jason.swails@gmail.com1, Özlem Demir2, Gustavo de M. Seabra, seabra@qtp.ufl.edu2, and Adrian E. Roitberg2. (1) Chemistry Department, State University of New York at Binghamton, 144 Sheedy Rd., Vestal, NY 13850, (2) Department of Chemistry, Quantum Theory Project, University of Florida, PO Box 118435, Gainesville, FL 32611-8435
Chagas' disease is an incurable and lethal chronic disease prevalent in Central and South America and is transmitted by insects carrying the infectious protozoan, Trypanosoma cruzi. This pathogen is responsible for the devastating effects of Chagas' disease and, as such, is the target for possible therapies. Instrumental to T. cruzi's survival is its trans-sialidase enzyme. Trans-sialidase removes sialic groups from sugar chains emanating from the host cells' membranes and reattaches them to the membrane of the protozoan. Because sialic groups are instrumental in cell recognition, T. cruzi is effectively able to evade immune response. Since trans-sialidase is not expressed in humans, it presents a good target for inhibition. Utilizing mixed QM/MM methodologies, a reaction simulation is carried out to elucidate the mechanism of the reaction at the active site of this enzyme. By determining the reaction mechanism, transition states can be isolated and inhibitors more effectively designed.