Structural insights into the discrepant synergistic activity of Codlemone and (Z)-8-dodecenol towards Grapholita molesta pheromones

BACKGROUND: Insect pheromone synergists have been widely used to produce potent pheromone products for environmentfriendly pest control. Codlemone (Cod) and (Z)-8-dodecenol (Dod) are two major Grapholita molesta pheromone synergists, with Cod having greater synergism and affinity for G. molesta pheromone binding protein 2 (GmolPBP2). Uncovering structural information key to the different binding affinity of Cod and Dod to GmolPBP2 would gain insights into what causes their synergy activity discrepancy. RESULTS: Binding modes of the two synergists in the binding pocket of GmolPBP2 were analyzed and compared by molecular dynamics-based approaches. Although Cod and Dod were stabilized in a similar hydrophobic pocket, their interaction details with GmolPBP2 were divergent due to the extra double bond (C10 = C11) in Cod. The C10 = C11 improved the hydrophobic interactions of Cod with around residues. Such hydrophobic interaction improvement was also reflected in the raised importance of Phe11 in the GmolPBP2-Cod interaction. Not only that, the increased hydrophobic forces introduced by the C10 = C11 changed the CH2-OH orientation in the GmolPBP2-Cod complex, which improved the H-bond interaction. Electrostatic complementarity analysis further indicated the positive role of C10 = C11 in optimizing GmolPBP2-Cod interaction. CONCLUSION: The C10 = C11 is thought to contribute greatly to Cod's stronger synergy as a group key to the higher GmolPBP2-affinity, based on which the improvement directions for Cod and Dod were addressed as well. Our findings will aid in the development and optimization of more effective pheromone synergists, resulting in more effective pheromonebased pest management. (C) 2022 Society of Chemical Industry.