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

BACKGROUND: Cydia pomonella is known as a worldwide quarantine fruit pest, causing great damage to fruit production every year. Sex pheromone mediated management has been widely used in the control of C. pomonella. 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. Detailing the interactions between Dod and its transporter protein, C. pomonella pheromone binding protein 2 (CpomPBP2), would provide inspiration for chemical optimization to improve the synergistic effects of Dod. RESULTS: In the present 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 hydrophobic residues including 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. Due to 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. Not only that, interactions negative to the binding of Dod were described as well. CONCLUSION: The present research detailed the discovery of key residues involved in the CpomPBP2-Dod interactions. Our results would provide guidance and cautions for the prospective discovery, optimization, and design novel chemicals with similar or stronger synergistic effect to codlemone in controlling C. pomonella. This article is protected by copyright. All rights reserved.