Pathway-Based Analysis of Essential Metabolic Enzymes as Drug Targets

Abstract

Tuberculosis (TB) , caused by Mycobacterium tuberculosis , remains a major global health crisis, aggravated by rapid emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains. Conventional drug discovery is time-consuming and expensive, making computational target identification and drug repurposing as crucial strategies to accelerate the development of novel antitubercular therapies. This study aimed to identify and prioritize the metabolic enzymes as potential drug targets through pathway based analysis and to screen the FDA-approved drug library for potential canidates for drug repurposing. Based on the pathway analysis, para-aminobenzoate synthase component I (PabB) was selected as a potential drug target owing to its role in folate biosynthesis. Subesquently, an FDA-approved drug library was screened based on ADMET properties and selected compounds were used for molecular docking agaist the protein. Molecular docking through DiffDock and validation using GNINA revealed that Ligand 5 and Ligand 27 exhibit favourable interaction profiles within the binding region of PabB, and emerged as potential candidates for further investigation in drug repurposing. The identification of PabB protein asan essential metabolic drug target, coupled with screening of FDA-approved drugs as inhibitors, provides a promising framework for anti tubercular drug discovery.