Integrating Molecular Docking and Electrophysiology Reveals Sesquiterpenes as Candidate Attractants for Ceratitis capitata Wiedemann (Diptera: Tephritidae)

The Mediterranean fruit fly (Ceratitis capitata) is a globally invasive pest that affects a wide range of fruit and vegetable crops. Identifying cost-effective attractants is essential for sustainable integrated pest management (IPM). This study explored whether molecular docking, combined with electrophysiological recordings, can help prioritize structurally diverse compounds with potential relevance to medfly olfaction. We assessed the predicted interactions of more than 100 attractant-related and semiochemical compounds, including multiple stereoisomers, with 14 odorant-binding proteins (OBPs) and four odorant receptors (ORs). Trimedlure served as a benchmark ligand. Docking suggested that several sesquiterpenes may interact favorably with subsets of OBPs and ORs, although these predictions require biochemical validation. A small set of compounds with high predicted affinity, readily available in the laboratory, was further examined using electroantennography (EAG), which confirmed that selected sesquiterpenes elicited peripheral antennal activation in irradiated males. Overall, our results demonstrate the utility of computational screening as an exploratory tool for prioritizing candidate ligands and generating hypotheses about chemosensory processing in C. capitata. Integrating molecular modeling with biochemical and behavioral validation is a promising approach to developing next-generation IPM attractants.