Tularemia is a potentially fatal bacterial disease caused by Francisella tularensis , prevalent in North America and across northern Europe and Asia. The outer membrane lipoprotein Flpp3 has been identified as both a virulence factor and a promising target for subunit-based vaccine development. Structural analysis of Flpp3sol reveals a distinctly polarized surface, with regions of strong positive and predominant negative charge, and a hydrophobic internal cavity formed primarily by an elongated loop. 1,2 To explore potential therapeutic interventions, we computationally assessed the binding affinity of candidate drug molecules from the ZINC database 3 to the protein cavity, obtaining docking energies. Experimentally, we expressed and purified Flpp3sol to prepare it for further experimental investigations of the binding interactions by NMR. Future work will involve analyzing the docked compounds, selecting promising candidates via principal-component analysis (PCA), and characterizing their structural and dynamic interactions with the protein using NMR spectroscopy. This integrated computational and experimental approach aims to identify and characterize potential drug candidates targeting Flpp3, providing insights for rational drug design against F. tularensis .
M. Asgari (2026) studied this question.