Unravelling the molecular recognition mechanism between odorants and PBP1 in Loxostege sticticalis by homology modelling, molecular docking, and MD simulation

Pheromone-binding proteins (PBPs) help insects communicate effectively and regulate social behaviour by binding and transporting odorants. However, the precise atomic-level interactions of PBP1 in Loxostege sticticalis (LstiPBP1) with odorants remain poorly understood. Therefore, the three-dimensional structure of LstiPBP1 was constructed using homology modelling, after which complex structures of LstiPBP1 with six odorants (cis-3-hexenyl acetate, naphthalene, heptaldehyde, phenethyl alcohol, α-ionone, and (E)-11-tetradecenol), respectively, were obtained by molecular docking. Each complex underwent molecular dynamics simulations to investigate their detailed interactions. In silico site-directed mutagenesis was performed on the key residues to verify the accuracy of the simulation models. Energy analysis and interaction patterns revealed that hydrophobic interactions, mainly stemming from van der Waals interactions, are critical for the interaction between LstiPBP1 and these odorants. Additionally, hotspot residues on LstiPBP1 involved in interacting with different odorants were identified, providing further insight into the specific molecular interactions that govern their recognition. These results facilitate the development of inhibitors targeting the insect olfactory system.