Targeting Antibacterial Resistance: Computational Exploration of Bioactive Compounds in Dipsacus asper Integrating Docking, ADMET Analysis, and Molecular Dynamics Simulations

ABSTRACTNatural compounds derived from plants offer a sustainable and promising solution to the global challenge of antimicrobial resistance. This study focuses on Dipsacus asper (D. asper), a plant traditionally used in Chinese medicine, and investigates its bioactive potential to identify novel antibacterial agents. Leveraging comprehensive in silico analyses, 44 compounds previously isolated from D. asper were evaluated for their binding affinities against four key bacterial proteins: DNA gyrase B, tyrosyl‐tRNA‐synthetase, penicillin binding protein 2X (PBP2X), and penicillin binding protein 4 (PBP4). This integrated approach, combining molecular docking, ADMET profiling, DFT, and MESP studies, identified dipsalignan, cantleyoside, triplostoside A, and dipsanoside N as leading candidates. Dipsalignan demonstrated superior bioavailability and distinct electronic properties influencing its reactivity. Molecular dynamics (MD) simulations validated the stability of protein–ligand interactions, with RMSD and RMSF analyses confirming equilibrium under physiological conditions. Binding free energy calculations revealed that van der Waals and hydrophobic interactions are critical in enhancing inhibitory potential. Biological significance was evident as the computationally identified compounds align with essential criteria for effective antibacterial agents, warranting further in vitro and in vivo studies. This research underscores the unique potential of D. asper‐derived compounds to address antimicrobial resistance and presents a robust framework for discovering plant‐based antibacterial agents. By expanding the repertoire of natural product‐based therapeutics, this study lays the foundation for future experimental validation and therapeutic applications.