HIGH-THROUGHPUT VIRTUAL SCREENING OF AFFINE INTERACTIONS OF A FLUORESCENT OLEYLAMINE DERIVATIVE WITH PROTEIN TARGETS OF SEVERAL INSECTS.

Computer-aided docking with Alphafold-based protein structure modeling revealed the affinity of the ligand DOLA ((Z)-5-(dimethylamino)-N-(octadec-9-en-1-yl)naphthalene-1-sulfonamide) to key metabolic proteins of insects (Tenebrio molitor, Tribolium castaneum, Locusta migratoria, Lucilia cuprina, Drosophila melanogaster). Affine interactions were found with cytochrome P450 family CYP6 (Ebind -10.4 to -8.9 kcal/mol), which participate in detoxification, hormone and xenobiotic metabolism: CYP6BK19, CYP6a23-like, CYP6FD3, CYP6t1, CYP6g1, CYP6t3, CYP6v1, CYP6a18; and cytochrome P450 family CYP4 (Ebind -10.1 to -8.3 kcal/mol), which participates in fatty acid and foreign compound metabolism: Cyp4aa1, CYP4c3-like, CYP4G102, CYP4G62, CYP4g15, CYP4d, CYP4Q33, CYP4G123.
DOLA also interacted with long-chain fatty acid-CoA ligase (Ebind = -10.0 kcal/mol), fatty acyl-CoA reductases (Ebind -9.7 to -8.2 kcal/mol), CYP18a1 (Ebind = -9.2 kcal/mol), lipocalins (Ebind -8.6 to -8.2 kcal/mol), and fatty acid desaturases (Ebind -8.5 to -8.2 kcal/mol), involved in the metabolism, transport and storage of fatty acids, synthesis of cuticular components, pheromones, and metabolism of ecdysone.
DOLA has been identified as a potential affine ligand for several P450 and fatty acid-converting enzymes. These in silico results will contribute to our understanding of insect biochemistry and will serve as a foundation for further experimental in vitro studies of this compound as a tool for investigating insect metabolism or as a potential population regulator.

Supported by Ministry of Education grant No. 20250893 and State Program for Scientific Research No. 20210560.