Inhibiting outer membrane protein synthesis in Gram‑negative bacteria represents an important strategy for developing novel antibacterial agents. Darobactin (DA) can selectively bind to the outer membrane protein BamA, yet its structural complexity limits scaffold optimization. In this study, we employed pharmacophore hypotheses and scaffold screening to identify novelβ‑strand mimetics capable of reproducing the key binding geometry of DA. Based on the crystal structures of BamA–DA complexes, a full macrocyclic pharmacophore model (DA‑BCm) was constructed and deconstructed into two sub‑models: the side ring (DA‑SRm) and the middlering (DA‑MRm). Through Enamine database virtual screening, diyne‑probe validation, SciFinder scaffold expansion, and evaluation of literature‑derived cyclic peptides, our results demonstrated that DA‑SRm exhibits high specificity for the β‑strand backbone geometry and can guide the discovery of mimetics independently of the DA scaffold. Compound 2 (CAS14642‑97‑8) showed perfect matching of all five pharmacophore features in its global minimum energy conformation. Compound 8 (Biphenomycin B), in its outward orientation, matched all five features and formed three hydrogen bonds. After conjugation with Compound 2 via anamide bond, the resulting hybrid derivative stably matched key pharmacophore features in low‑energy conformations and formed up to four hydrogen bonds. This study provides acomputational basis for subsequent synthesis and biological evaluation, highlighting Compound 2 and Compound 8 derivatives as potential novel BamA binders.