Computational Protein Structural Annotations of <i>Mycobacterium tuberculosis</i> Thiamine Phosphate Pyrophosphorylase

Background Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a respiratory infection characterized by persistent lung infection. The development of drug resistance in Mtb poses a significant challenge in treating TB patients, necessitating the discovery of new therapeutic targets. Materials and methods In this study, bioinformatic methods were employed to investigate the structure and function of Mtb-Thiamine phosphate pyrophosphorylase (TPPase) at a molecular level. As an X-ray/nuclear magnetic resonance crystallographic structure was unavailable in the protein databank, a homology protein model of TPPase was created using the X-ray structures of TPPase as templates, following homology modelling method. The resulting Mtb-TPPase protein structure was assessed for quality, including stereochemical prediction using Ramachandran plot, Procheck, and Prosa. Key structural and functional residues of Mtb-TPPase were identified using the crystal structure of TPPase. Results The homology model of TPPase, constructed using the above-mentioned methods, exhibited a high-quality protein structure that satisfied stereochemical predictions. The model retained the topological and functional properties of the TPPase protein family. The Mtb-TPPase model demonstrated suitability for molecular interactions, such as drug-protein interactions, as indicated by energy and Ramachandran plot values. These findings provide valuable insights for designing TPPase inhibitors and structure-based drug design approaches. Conclusion The constructed homology model of Mtb-TPPase presents a tertiary structure that can be utilized for designing selective and specific Mtb-TPPase inhibitors. However, further investigations involving computational docking and high-throughput screening experiments are required to gather more detailed information and validate the model's potential applications.