Fig 1.
Chemical structures of the tested compounds: (A) TM, (B) SA, and (C) SLS.
Fig 2.
Preliminary antimicrobial activity of TM, SA, SLS, and NC against the tested pathogens.
Representative zone-of-inhibition images are shown for (A) S. aureus ATCC 29213, (B) S. aureus-CI, (C) MRSA-1, (D) MRSA-2, (E) S. saprophyticus ATCC 43867, (F) S. epidermidis ATCC 12228, (G) S. pyogenes-A ATCC 19615, (H) S. pneumoniae ATCC 49619, (I) E. faecalis ATCC 29212, (J) B. cereus ATCC 10876, (K) E. coli ATCC 25922, (L) K. pneumoniae ATCC 27736, (M) P. aeruginosa ATCC 9027, (N) S. typhimurium ATCC 13311, (O) S. flexneri ATCC 12022, (P) P. vulgaris ATCC 6380, (Q) P. mirabilis ATCC 29906, (R) C. albicans ATCC 10231, and (S) A. niger ATCC 6275. All assays were performed using three independent biological replicates (n = 3).
Table 1.
Summary of protein–ligand interactions for the top-scoring docked complexes. Hydrogen-bonding residues, hydrophilic and hydrophobic contacts, salt bridges, and water-mediated hydrogen bonds were identified using a Python-based interaction analysis pipeline inspired by PLIP. π–π stacking interactions are reported where present based on visual inspection of interaction maps. Distances are reported in Å, and ranges indicate multiple contacts involving the same residue. Hydrophobic residues correspond to non-polar ligand–protein contacts (C···C/S interactions), whereas hydrophilic residues represent hydrogen bond donors/acceptors or charged side chains contributing to polar interactions. n denotes the number of individual hydrogen bonds or salt-bridge contacts contributed by a given residue.
Fig 3.
Heatmap of molecular docking scores for TM, PA, and LS against all target proteins.
Lower docking scores indicate stronger predicted binding affinity. The heatmap summarizes the comparative binding strengths of each compound across the full protein panel.
Fig 4.
Molecular interaction analysis of TM with selected microbial target proteins.
Combined 2D and 3D binding interaction representations illustrating the binding mode, key stabilizing interactions, and active-site accommodation of TM within: (A) β-carbonic anhydrase (PDB: 5CXK), (B) cell division protein FtsZ (PDB: 4DXD), and (C) sterol 14-α-demethylase (PDB: 5TZ1). The 2D interaction maps highlight hydrogen bonding, hydrophobic contacts, and aromatic interactions, whereas the corresponding 3D views depict TM within the respective binding pockets, demonstrating stable, target-specific binding conformations.
Fig 5.
Molecular interaction analysis of PA with selected microbial target proteins.
Combined 2D and 3D binding interaction representations illustrating the binding mode, key stabilizing interactions, and active-site accommodation of PA within: (A) β-carbonic anhydrase (PDB: 5CXK), (B) DNA topoisomerase IV, B subunit (PDB: 4URN), and (C) sterol 14-α-demethylase (PDB: 5TZ1). The 2D interaction maps highlight hydrogen bonding, hydrophobic contacts, and aromatic interactions, whereas the corresponding 3D views show PA positioned within the respective binding pockets, demonstrating stable, target-specific binding conformations.
Fig 6.
Molecular interaction analysis of LS with selected microbial target proteins.
Combined 2D and 3D binding interaction representations illustrating the binding mode, key stabilizing interactions, and active-site accommodation of LS within: (A) peptide deformylase (PDB: 1LMH), (B) lipid A deacetylase LpxC (PDB: 2VES), and (C) serine/threonine phosphatase Z1 (PDB: 5JPF). The 2D interaction maps highlight hydrogen bonding, hydrophobic contacts, and electrostatic interactions, whereas the corresponding 3D views depict LS within the respective catalytic pockets, demonstrating stable, target-specific binding conformations.
Fig 7.
Heatmap comparing MM/GBSA binding free energies (ΔG) and estimated dissociation constants (Kd) for selected protein–ligand docked complexes.
Lower (more negative) ΔG values and smaller Kd values indicated stronger predicted binding affinities across the evaluated complexes.