ABSTRACT: Helicobacter pylori (Hp), a Class I carcinogen infecting over 50% of the global population, is increasingly resistant to conventional antibiotics. This study presents an AI-engineered probiotic strategy targeting urease, a key Hp virulence factor. A humanized single-domain antibody (UreBAb), previously identified and selected in our laboratory, was synthesized commercially and modeled using AlphaFold2, with structural validation conducted via SAVES 6.0. Molecular docking (PyMOL/ClusPro2) and binding energy analysis (InterProSurf) identified critical urease-active residues: K40, P41, K43, E82, F84, T86, K104, I107, K108, and R109. Machine learning-guided optimization using mCSA-AB, I-Mutant, and FoldX prioritized four mutational hotspots (K43, E82, I107, R109), leading to the generat
