Antibiotic Resistance: Mechanisms of Drug Failure and Role of Molecular Docking in Antibiotic Development
İrem Ünlü
09/09/2026
The rapid rise of antimicrobial resistance (AMR) is a serious global health crisis that compromises the effectiveness of conventional antibiotic treatments. This paper describes the main biochemical targets of antibiotics, such as peptidoglycan assembly, ribosomal protein synthesis, and nucleic acid replication, and the evolutionary strategies of bacterial resistance. The main mechanisms of bacterial resistance are enzymatic inactivation, target modification, active efflux systems and decreased outer-membrane permeability. However, traditional drug discovery is often not able to keep pace with evolving pathogens, and computational biology has become an integral part of modern therapeutic research. In particular, this review is focused on molecular docking as a structure-based approach to pre-screen chemical libraries, predict binding orientations and evaluate protein-ligand interactions. As an example of the computational procedure, a docking study of ciprofloxacin with Escherichia coli DNA gyrase B was carried out with SwissDock and visualized with PyMOL. The simulation demonstrated encouraging binding scores and specific interaction distances within the target's binding pocket. The integration of computational tools with a thorough understanding of the bacterial resistance mechanisms will ultimately be the key to an acceleration of the discovery and development of new and robust antibacterial agents.