TROPIC: An Integrative Approach Aimed at Identifying Drug Targetable Human- Parasite Interactions - Burcu Ozden; Ezgi Karaca; Beyza Kaynarca (2024)
Parasitic diseases, predominantly prevalent in underdeveloped countries and impacting young children, present a significant global concern with substantial socioeconomic impacts. Unfortunately, combating these diseases is challenging due to limited pharmaceutical options and drug resistance. Therefore, understanding host-parasite protein-protein interactions at the molecular level may contribute to identifying new targets for the prevention or treatment of infections (Arnold et al., 2012; Cuesta-Astroz and Oliveira, 2018). In this context, TROPIC approach integrates pathogen genomics and structural modeling to explore targetable, new host-parasite interactions. TROPIC was built upon Dr. Cuesta-Astroz's study (Cuesta Astroz et al., 2019a) unraveling human-parasite interactomes in 15 parasites. In this set, we focused on 276 domain-domain interactions at the most central nodes of 15 eukaryotic parasites (T. spiralis, T. gondii, T. brucei, S. mansoni, P. vivax, P. knowlesi, L. infantum, L. donovani, L. braziliensis, C. parvum, G. lamblia, T. cruzi, P. falciparum, C. hominis, and L. mexicana) and employed domain-domain host-parasite interaction modeling using AlphaFold2-Multimer v2.2. The modeling of human-parasite interactions was conducted on the Turkish National Computation Resources (TRUBA). The generated models and their scores are uploaded here. Our methodology is described at https://github.com/CSB-KaracaLab/TROPIC
Keywords: cc-by-nc-4.0; host-parasite; alphafold; prediction; druggable