Computational evaluation of selected compounds as potential inhibitors of gastric H⁺/K⁺-ATPase using molecular docking, molecular dynamics simulations, MMGBSA, and ADMET analyses

This study investigated the inhibitory potential of selected phytochemicals and conventional drugs against gastric H⁺/K⁺-ATPase, an important therapeutic target associated with acid-related gastrointestinal disorders such as peptic ulcers and gastroesophageal reflux disease. Computational approaches, including molecular docking, molecular dynamics simulations, MMGBSA free energy calculations, and ADMET profiling, were employed to evaluate the pharmacological relevance of the selected compounds. Molecular docking analysis revealed that several compounds exhibited favorable interactions with the target enzyme, with ciprofloxacin demonstrating stronger binding affinity than 3-hydroxypropyl oleate in both active-site and blind docking studies. Interaction analyses further showed that ciprofloxacin formed stable hydrogen bonds, hydrophobic interactions, and attractive charge interactions within the enzyme binding pocket. Molecular dynamics simulations confirmed the superior structural stability of the ciprofloxacin-protein complex through lower RMSD, RMSF, RoG, and SASA values compared with 3-hydroxypropyl oleate. Although MMGBSA calculations indicated slightly stronger total binding free energy for 3-hydroxypropyl oleate, ciprofloxacin displayed better overall compactness and interaction stability throughout the simulation period. ADMET and pharmoglyph analyses further established ciprofloxacin as the more promising candidate due to its favorable drug-likeness, high gastrointestinal absorption, acceptable solubility, lower metabolic risks, and excellent PharmoScore. The integrated computational findings suggest that ciprofloxacin possesses significant inhibitory potential against gastric H⁺/K⁺-ATPase and may serve as a promising scaffold for the development of safer and more effective anti-ulcer therapies.