Towards In Silico 3-D Structure Modeling and Prioritization of Candidate Genes Regulating the Bovine and Caprine Apelinergic System

Abstract

Abstract Background The Apelinergic system (consisting of two ligands - APELIN/APELA and its receptor APJ) plays a crucial role in many important biological processes in animals. The human Apelin, Apela and its receptor APJ are well characterized in terms of structure and function, but very little is known about the two ligands and its receptor in bovines and caprine species. The genes related to the Apelinergic system and their roles in various metabolic processes are also understudied in terms of livestock such as bovine and caprine species. Therefore, the aims of the present were to a) model the 3-D structure of the Apelinergic system and b) identify and prioritize the candidate genes regulating the system in bovine and caprine species through state of art bioinformatics tools. A three-dimensional model (3D) was constructed using SWISS-Model, a homology modeling server. The predicted model was validated by SAVES including PROCHECK and ERRAT server. The structures were refined by Refold server of intfold homology modeling tool. Python molecular viewer (PyMol) was used to visualize the tertiary structure of the protein. Three gene prioritizing tools Genie, toppgenet, David, and Genemania to further visualize the network of genes were used.Results The overall quality factor for the remodeled 3D structure for the three best templates selected for both bovine and caprine species was found to be 97.95, 97.82 and 96.40%. We identified and prioritized the top 10 most important genes related to each of the ligands (Apelin/apela and their receptor APJ) and the top 20 neighboring genes for both bovine and caprine species. The top 10 most common genes that interacted with the Apelinergic system in bovines and caprines are FLT1, ADIPOR1, ADIPOR2, ADIPOQ, INS, LEP, KDR, AKT1, TGFB1, NOS3, EGFR1, IGFR1, VEGFA, EGFR, FGF2, MAPK1/3, PPARG, PPARD, and APLNR.Conclusion The models generated in the present study can be used as a foundation for future drug-designing strategies and experiments. The result of the study may be a guiding point for further investigations on the role of the Apelinergic system in various physiological processes in bovines and caprine species.