Structure-based analysis from cestodes’ FABPs towards virtual screening campaigns

SANTIAGO RODRÍGUEZ; GAVERNET, LUCIANA; TALEVI, ALAN; FRANCHINI, GISELA R.

Congreso; XLIX Reunión Anual de la Sociedad Argentina de Biofísica (SAB); 2021

Echinococcosis and Cysticercosis are listed among WHO’s list of Neglected tropicaldiseases (NTD’s), affecting people in tropical and subtropical areas.Echinococcusgranulosus andEchinococcus multilocularis are the causative agents of cystic andalveolar echinococcosis, respectively, whileTaenia solium is the parasitic agent involved incysticercosis.In general, cestodes present an incomplete lipid metabolism lacking many enzymesinvolved in the synthesis, so they must obtain these molecules from their hosts. In thissense, Fatty Acid Binding Proteins (FABPs) have been proposed as essential for cestodes’life cycle, because they are small intracellular proteins that bind fatty acids and otherhydrophobic ligands, being important in lipid traffic and delivery of such compounds.In the present study we propose the tertiary structure of FABPs fromE.granulosus,E.multilocularis andTaenia solium, obtained fromin silico methodologies such asHomology Modelling (HM) and Molecular Dynamics (MD). Each model generated by HMwas validated using the knowledge-based potential QMEAN4 and Ramachandran Plotanalysis.On the other hand, MD simulations allow us to analyze the dynamic evolution of an atomicsystem and its interactions in a certain time period. From each validated-model, weperformed 200 ns Molecular Dynamics Simulations with explicit water molecules. Full MDtrajectories were then submitted to a Principal Component Analysis (PCA) and k-meansclustering algorithm, in which we were able to obtain the main binding site conformersfor each FABP model.We developed 3D FABPs models for three clinical-relevant cestodes. This study will allowus to perform Molecular Docking protocols to carry out virtual screening campaigns usingdifferent drug databases in order to discover new potential compounds with biologicalactivity against these etiological agents.