Functional Annotation of Some Hypothetical Genes in the Schistosoma Parasite Based on Reciprocal Best -Structural-Hit Relationship

The Schistosoma parasite is responsible for some neglected tropical diseases. It has inflicted considerable financial damage on livestock and reports indicate its spread across the central regions of Iran's northern provinces. For an effective drug to be developed against this parasite, a comprehensive understanding of the functions of its genes is imperative. Currently, the functions of many genes in Schistosoma parasites remain unidentified, hindering their recognition. Traditional methods for functional annotation rely on protein sequence similarity. However, this approach is not always sensitive enough to catch the similarities between two remotely related proteins. Studies have indicated that incorporating protein structure into the function prediction process can aid in the identification of unknown proteins. In our research, we employed two cutting-edge tools, Alphafold and Foldseek, to predict the functions of hypothetical proteins in the Schistosoma parasite. To achieve this, we compared the protein structures of the proteins of a Schistosoma parasite and proteins of Caenorhabditis elegans, the closest model organism to Schistosoma, using Foldseek to find the reciprocal best-hit relationships. As part of our investigation, we delved deeper into two specific predictions, analyzing evidence for functional similarity like interaction patterns between proteins and similarities in functional domains. Our findings suggest that one of the genes studied likely plays a role in embryogenesis, while the other may be associated with the egg-laying process of the Schistosoma parasite. The latter gene, in particular, merits further exploration as a potential drug target.