De Novo Design of High-Affinity Miniprotein Binders Targeting Francisella Tularensis Virulence Factor.

ABSTRACT: Francisella tularensis poses considerable public health risk due to its high infectivity and potential for bioterrorism. Francisella-like lipoprotein (Flpp3), a key virulence factor unique to Francisella, plays critical roles in infection and immune evasion, making it a promising target for therapeutic development. However, the lack of well-defined binding pockets and structural information on native interactions has hindered structure-guided ligand discovery against Flpp3. Here, we used a combination of physics-based and deep-learning methods to design high-affinity miniprotein binders targeting two distinct sites on Flpp3. We identified four binders for site I with binding affinities ranging between 24-110 nM. For the second site, an initial binder showed a dissociation constant (K_D

SUBMITTER: Gokce-Alpkilic G 

PROVIDER: S-EPMC12723454 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature