A metal-aware library-expansion and virtual-screening workflow for Pseudomonas aeruginosa ATCC 15692 (PAO1) MraY identifies compound 5311309 with stable binding and mid-micromolar activity

Introduction: ); therefore, metal coordination is critical for reliable structure-based prioritization. Methods: ADMET. Results: Three hits (6675, 2733768, 5311309) were prioritized. In microsecond MD, compound 5311309 showed the most stable pose and key hotspot retention. ADMET indicated a permeability/efflux bottleneck along with liver-kidney and irritation/sensitization alerts, whereas hERG and AMES signals were favorable. In growth assays, compound 5311309 showed an IC50 of approximately 15.1 μM and an MIC of 64 μM. Conclusion: Metal-aware pocket modeling plus multi-level screening improved plausibility and ranking for this metal-dependent target, identifying compound 5311309 as a practical lead optimization starting point.