Structure dynamics reveal key residues essential for the sense of 1-dodecanol by Cydia pomonella pheromone binding protein 2 (CpomPBP2)

Cydia pomonella, a worldwide quarantine fruit pest, causes great damage to fruit production every year. Sex pheromone-mediated control of C. pomonella has been widely used. As an indispensable ingredient of commercial sex attractants, 1-dodecanol (Dod) works to synergize the effect of codlemone in attracting male moths of C. pomonella. The interactions between Dod and its transporter protein, C. pomonella pheromone-binding protein 2 (CpomPBP2), provide inspiration for chemical optimizations to improve the synergistic effects of Dod.

In this research, molecular simulations and biological verifications were used in combination to uncover key residues in CpomPBP2 essential for sensing Dod. After performing 150 ns molecular dynamics (MD) simulations, the C1-C12 chain of Dod was found to be locked by the van der Waals energy contributed by the hydrophobic residues Phe12, Leu68, and Ile113, whereas the -OH part of Dod was anchored by the H-bond derived from Glu98 and the salt-bridge derived from Arg109. Because of the importance of these two electrostatic interactions, Glu98 and Arg109 were further verified as key residues in determining the binding affinity between Dod and CpomPBP2. In addition, interactions unfavorable to the binding of Dod were described.

The research detailed the discovery of key residues involved in CpomPBP2-Dod interactions. Our results provide guidance and caution for the prospective discovery, optimization, and design of novel chemicals with a similar or stronger synergistic effect to codlemone in controlling C. pomonella.