Novel protocol for reverse docking in Neglected Tropical Diseases incorporates local frustration as a predictor of biological relevance

CLEMENTE CAMILA M; LEONETTI CESAR O; RAVETTI S; PARRA R GONZALO; FREIBERGER MARÍA INÉS

Buenos Aires VIRTUAL

Congreso; 1st Congress of Women in Bioinformatics and Data Science Latin America; 2020

CONICET

According to the World Health Organization (WHO), Leishmaniasis, Chagas and Malaria diseases are Neglected Tropical Diseases (NTDs). The etiological agents that cause these diseases are different protozoa that result in more than thousands of deaths in the world, mostly in poor populations without access to appropriate health services and sanitation. In recent years, in silico studies began to play an important role in drug discovery. One of the most important challenges in drug design is target identification and neglected diseases are not an exception. In this work, we present a new protocol that provides a simple and fast way to perform a reverse docking. This new protocol offers a database developed with all reported protein structures of Leishmania spp., Trypanosoma spp. and Plasmodium spp.. This database has the annotation of all predicted druggable pockets (DrugScore ≥ 0.5) of each protein structure and the frustration value for each selected pocket. To perform the reverse docking, this protocol uses the annotations of this database and a ligand structure. As a result, (1) protein-ligand binding energies, (2) types of protein-ligand interactions, and (3) the identification of amino acids involved in the protein-ligand interaction are given.It is important to highlight that this protocol provides 3D interaction visualization per binding site for manual inspection and the frustration index that can be used as an indicator of the biological activity of the pocket. This new protocol is expected to be a powerful resource for researchers working on drug design for these NTDs.