Structural Insights into Two Representative Conformations of the Complex Formed by Grapholita molesta (Busck) Pheromone Binding Protein 2 and Z-8-Dodecenyl Acetate

Abstract

Grapholita molesta is a notorious fruit borer globally, causing severe damage to fruit production. To control the pest, one commonly used mean is pheromone-mediated management. As an important sex pheromone, Z-8-dodecenyl acetate (Z8–12: Ac), is often coformulated with other active ingredients to regulate the behavior of G. molesta. To uncover its interactions with G. molesta pheromone binding protein 2 (GmolPBP2) is used to help develop insect attractants. During 200 ns molecular dynamics simulations, two representative conformations of the GmolPBP2-Z8–12: Ac complex are selected. Conformation II at the time of 14–106 ns is dominantly maintained by the hydrophobic interactions and hydrogen bond. In Conformation I, which lasts from 106 to 200 ns, the hydrophobic interactions are enhanced while the hydrogen bond is quite weakened, due to the formation of a more sophisticated hydrophobic binding pocket and the enlargement of hydrogen bond distance. Taking the two conformations as a whole, the affinity between GmolPBP2 and Z8–12: Ac is crucially determined by three hot-spots including Phe11, Trp36, and Ile51. These results would provide a basis for the discovery, optimization, and design of leading compounds potentially active to attract G. molesta.

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

“…Acquisition of a reliable conformation is of great significance for subsequent experiments, including binding mode analysis, binding free‐energy calculation, free‐energy decomposition, and hot‐spot determination. As in other research on the structure of insect OBPs, 26,51,52 van der Waals (Δ E vdW ) and electrostatic energy (Δ E ELE ) were two dominant driving forces in the formation and maintenance of the CpomPBP2–Dod complex. As shown in Table 1, Δ E vdW and Δ E ELE values were as high as −34.83 and − 7.78 kcal mol –1 , respectively.…”

“…Confirmation of Glu98 as a hot‐spot supports the assumption that residues forming H‐bond with ligands are usually crucial to the protein‐ligand interactions 24,32,51 . As a matter of experience, in protein‐ligand interactions involved with insect OBPs, key residues are usually those forming either H‐bond or hydrophobic interactions with ligand groups 26,32,44,53 . However, Arg109 providing a salt‐bridge interaction, a form of electrostatic interaction rarely described in protein–ligand interactions involved with insect OBPs, was determined as a second key residue for the CpomPBP2–Dod complex.…”

“…To prepare for MD simulations, the CpomPBP2–Dod model was immersed in a rectangular box of explicit transferable intermolecular potential with 3 points (TIP3P) water with a minimum solute wall distance of 8 Å 25 . Na + ions were added to keep the entire system neutral 26 . The parameters and charge of the Dod ligand were optimized using General Amber Force Field (GAFF) and AM1‐BCC (semi‐empirical (AM1) with bond charge correction (BCC)) methods, and counterparts for the protein CpomPBP2 were set using ff9SB 27–29 .…”

“…Purified CpomPBP2 protein was kept at −80 °C for further tests. Expression and purification of mutant CpomPBP2 (CpomPBP2MT) proteins were performed similarly 26 …”

Variability of Gut Microbiota Across the Life Cycle of Grapholita molesta (Lepidoptera: Tortricidae)

“…The oriental fruit moth, Grapholita molesta (Busck; Lepidoptera: Tortricidae), a major pest of Rosaceae fruit trees, is widely distributed throughout the fruit-growing regions of Asia, Europe, America, Australia, and Africa ( Dorn et al, 2003 ; Bellerose et al, 2007 ; Myers et al, 2007 ; Timm et al, 2008 ; Kirk et al, 2013 ). In China, it occurs in most of the fruit-growing regions except Tibet and can harm apple, pear, jujube, peach, plum, apricot, hawthorn, and other fruit trees by boring and feeding in twigs and fruits at larval stage, resulting in shoot dieback and fruit shedding ( Myers et al, 2006 ; Cao et al, 2015 ; Duarte et al, 2015 ; Tian et al, 2019 ). G. molesta undergoes multiple generations in a year and has the habit of host switching, which cause serious economic losses to the fruit industry every year ( Zheng et al, 2015 ).…”