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

RODRIGUEZ, SANTIAGO; GAVERNET LUCIANA; TALEVI ALAN; FRANCHINI GISELA

Congreso; XLIX Reunion anual de la sociedad argentina de biofisica; 2021

Echinococcosis and Cysticercosis are listed among WHO?s list of Neglected tropical diseases (NTD?s), affecting people in tropical and subtropical areas. Echinococcus granulosus and Echinococcus multilocularis are the causative agents of cystic and alveolar echinococcosis, respectively, while Taenia solium is the parasitic agent involved in cysticercosis. In general, cestodes present an incomplete lipid metabolism lacking many enzymes involved in the synthesis, so they must obtain these molecules from their hosts. In this sense, 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 other hydrophobic ligands, being important in lipid traffic and delivery of such compounds. In the present study we propose the tertiary structure of FABPs from E.granulosus, E.multilocularis and Taenia solium, obtained from in silico methodologies such as Homology Modelling (HM) and Molecular Dynamics (MD). Each model generated by HM was validated using the knowledge-based potential QMEAN4 and Ramachandran Plot analysis.On the other hand, MD simulations allow us to analyze the dynamic evolution of an atomic system and its interactions in a certain time period. From each validated-model, we performed 200 ns Molecular Dynamics Simulations with explicit water molecules. Full MD trajectories were then submitted to a Principal Component Analysis (PCA) and k-means clustering algorithm, in which we were able to obtain the main binding site conformers for each FABP model. We developed 3D FABPs models for three clinical-relevant cestodes. This study will allow us to perform Molecular Docking protocols to carry out virtual screening campaigns using different drug databases in order to discover new potential compounds with biological activity against these etiological agents.