Functional Annotation and Molecular Characterization of a Hypothetical Protein From Mycobacterium leprae Through In Silico Approaches: A Potential Therapeutic Target

Objective: Mycobacterium leprae causes leprosy, an infectious disease that has persisted over centuries and is still an issue in public health in many nations. Diverse bioinformatics techniques have been effectively employed to annotate the functions of hypothetical proteins (HPs) originating from different pathogenic bacteria. The objective of the current research was to elucidate the functions of an HP obtained from M. leprae. Methods: A variety of in silico tools were utilized to make predictions regarding the structure and function of this protein. To identify homologous proteins, the BLASTp program was used to search for sequence similarity across the available biological databases. Additionally, using the proper bioinformatics methods, a number of properties were determined, including physicochemical characteristics, subcellular localization, phylogenetic analysis, functional annotation, pathway analysis, protein-protein interaction, secondary and tertiary structure determination, active site detection, quality assessment analysis, molecular docking, pharmacokinetic and toxicity profiling, and further molecular dynamics simulations. Results: The HP exhibited putative biological activity associated with a conserved functional domain, the CTCD superfamily domain. The allophanate hydrolase activity of the chosen HP was predicted by the functional annotation. Pathway analysis demonstrated the protein’s involvement in cellular and metabolic processes. Numerous functional partners that play a crucial role in bacterial survival were identified through the chosen HP’s protein-protein interactions. Furthermore, active site prediction and molecular docking analysis of the HP with ligands indicated that it could be a therapeutic target for M. leprae. ADMET analysis indicated that the selected compound has favorable bioavailability, drug-likeness, and safety. The stability of these complexes was verified by molecular dynamics simulations, which suggests they have therapeutic potential. Conclusion: This study emphasizes the effectiveness of in silico methods in predicting the biological functions of HP and generating hypotheses for potential therapeutic targets.