Computational Investigation of Rhodomyrtus Tomentosa ‐Derived Compounds Targeting E. coli DNA Gyrase B via Molecular Docking, Molecular Dynamics, and ADMET

ABSTRACT

Antibiotic resistance in Gram‐negative bacteria, particularly Escherichia coli , has created an urgent demand for new antibacterial agents. Bacterial DNA gyrase, especially the ATPase‐active GyrB subunit, is an attractive yet underexplored therapeutic target. In this study, natural compounds from Rhodomyrtus tomentosa (Ait.) Hassk. were evaluated as potential DNA gyrase B inhibitors using integrated computational methods. Molecular docking validated by re‐docking with an RMSD value of 1.816 Å was employed to systematically screen natural compounds from R. tomentosa leading to the identification of 10 compounds including Viminalol, Friedelin, β‐Amyrin, Casuarinin, Furosin, Casuariin, 3‐p‐(E)‐Coumaroyloleanolic acid, rhodomyrtosone I, (2α,3β,4α)‐2,23‐Dihydroxy‐3‐ [[(2E)‐3‐(4‐hydroxyphenyl)‐1‐ oxo‐2‐propen‐1‐yl]oxy]olean12‐en‐28‐oic acid and 1,1',3,3',5,5'‐Hexahydroxy‐7, 7'‐dimethyl[2,2'‐bianthracene]‐9,9',10,10'‐tetrone, with stronger binding affinities than the reference inhibitor. Casuarinin (compound 38) exhibited the strongest affinity and formed stable interactions with key residues Asp73 and Gly77. Subsequent 200 ns molecular dynamics simulations demonstrated stable protein–ligand complexes, supported by consistent RMSD, radius of gyration, and solvent‐accessible surface area profiles. MMGBSA calculations confirmed the superior binding free energy of compound 38 (ΔG _total = −68.520 kcal/mol). ADMET predictions indicated generally favorable pharmacokinetic properties with low toxicity risks. These findings suggest that R. tomentosa ‐derived compounds represent promising lead candidates for the development of novel DNA gyrase B–targeted antibacterial agents for subsequent biological evaluation.