Homology Modeling of T. cruzi Squalene Epoxidase. Estimation of Ligand-Binding Affinities by MM-PSBA

GUIDO NOGUERA; LILIANA FINKIELZSTEIN; LUCAS FABIAN

Buenos Aires

Congreso; Fourth International Society for Computational Biology Latin America Bioinformatics Conference.; 2016

Analysis of lipid extracts from epimastigote of T. cruzi showed that some of TZHs synthesized by us produce squalene accumulation with a concomitant ergosterol deficiency by the probable squalene epoxidase (SE) inhibition.In this work, we present the resulting 3D model of SE-T cruzi constructed by homology modeling (Modeller 9.15 software) as a result of multiple alignments of aminoacid sequences using UCSF Chimera 1.10.1 software. Subsequently, to test this protein-model we performed free energy binding calculation for both TZHs and terbinafine (SE inhibitor) from a molecular dynamics simulation using the MM-PBSA method. Preliminary results suggest that this model is capable to discriminate between two sub-sets of compounds (squalene accumulators and non squalene accumulators). Finally, the target template constructed will be a valuable tool for a rational drug design of SE-T. cruzi inhibitors.