Structure-Based Prioritization and Dynamic Evaluation of Bepotastine as a Putative Binding Candidate for Mycobacterium bovis MurC

This repository contains the supporting computational data, molecular-modelling inputs, processed outputs, figures, and analysis scripts associated with the study entitled “Structure-Based Prioritization and Dynamic Evaluation of Bepotastine as a Putative Binding Candidate for Mycobacterium bovis MurC.” The study employed an integrated structure-based computational workflow to investigate UDP-N-acetylmuramate–L-alanine ligase from Mycobacterium bovis (Mb-MurC; PDB ID: 7BVA) as a potential small-molecule binding target. A library of 1,565 anti-infective compounds was subjected to structure-based virtual screening, physicochemical and ADMET filtering, molecular docking, protein–ligand interaction analysis, molecular dynamics simulations, MM-GBSA and MM-PBSA binding-energy estimation, residue-wise energy decomposition, principal component analysis, and projected free-energy landscape analysis. The docking protocol was assessed through redocking of the reference ligand into the ligand-bound Mb-MurC structure, PDB ID 7BVB. The redocked and crystallographic ligand poses produced a heavy-atom RMSD of 1.659 Å, supporting the ability of the docking procedure to reproduce the experimentally observed binding orientation. This value should be retained only if it was calculated directly between the crystallographic and redocked ligand poses. Bepotastine, bestatin, and olsalazine were selected for detailed molecular dynamics evaluation. Three independent 300-ns simulations were performed for the Mb-MurC–bepotastine complex. Bestatin and olsalazine were each evaluated using a single 300-ns trajectory and were therefore interpreted as descriptive comparators rather than replicate-supported systems. The repository includes, where generated and applicable: Prepared receptor and ligand structures Docking input and output files Redocking-validation files and superimposed ligand poses Molecular dynamics input files, topology files, and simulation parameters Representative structures and selected processed structural outputs RMSD, RMSF, radius of gyration, solvent-accessible surface area, hydrogen-bond, hydrophobic-contact, minimum-distance, and center-of-mass distance data MM-GBSA and MM-PBSA input and output files Residue-wise energy-decomposition results Principal component analysis and free-energy landscape outputs ADMET prediction results Final figures, compact supplementary tables, and curated analysis scripts The availability of individual analysis outputs may differ among simulation systems according to the analyses successfully completed and reported in the manuscript. Bepotastine was computationally prioritized as a putative Mb-MurC-binding candidate based on replicate-supported dynamic behaviour, favourable MM-GBSA/MM-PBSA binding-energy estimates, recurring protein–ligand interactions, and comparatively balanced predicted drug-like properties. Bestatin and olsalazine were retained as single-trajectory comparators and should not be interpreted as having the same level of replicate support. These computational findings do not establish direct MurC inhibition, target engagement, or antimycobacterial activity. Experimental confirmation will require biochemical enzyme-inhibition assays, direct-binding measurements, cytotoxicity testing, target-engagement studies, and whole-cell antimicrobial evaluation. This dataset is provided to support transparency, reproducibility, independent evaluation, and reuse of the computational workflow and results reported in the associated manuscript.