The Structural Basis of Binding Stability and Selectivity of Sarolaner Enantiomers for <i>Ctenocephalides felis</i> RDL Receptors.

ABSTRACT: The ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) is a key target for the development of antiparasitic agents, particularly against ectoparasites, such as fleas and ticks. Binding stability and selectivity of sarolaner enantiomers for Ctenocephalides felis RDL receptors (RDLR) were investigated in the current study. Wild-type (WT) C. felis RDLR and its A285S mutant were constructed using homology-based, fragment-based threading and AI-driven approaches, of which, SWISS-MODEL generated the most reliable structures. Molecular docking showed that the sarolaner S-enantiomer had higher binding affinity for both receptors than the R-enantiomer, primarily due to hydrogen bonding with Ile256, π-π stacking with Phe326, and hydrophobic interactions with Ile267 an

SUBMITTER: Zheng X 

PROVIDER: S-EPMC12250689 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature