title: Gypsy moth pheromone-binding protein-ligand interactions: pH profiles and simulations as tools for detecting polar interactions.
abstract: Pheromone-binding proteins (PBPs) are believed to control diffusion of pheromones in sensory hairs of insects. The interactions of gypsy moth (Lymantria dispar) PBPs with the sex attractant pheromone, (+)-Disparlure ((7R,8S)-epoxy-2-methyloctadecane), and the enantioselectivity of recognition are not completely understood. Enantioselectivity is important for L. dispar, because (-)-disparlure cancels the attraction of (+)-disparlure, so these moths use enantiopure (+)-disparlure for communication. We performed docking simulations of the protonated homology PBP models with the enantiomers of disparlure, 5-oxadisparlure, 10-oxadisparlure, 5-thiadisparlure and 10-thiadisparlure, together with a binding assay experiment, in which the pH profiles for the PBP-ligand combinations were surveyed. The molecular simulations revealed different amino acid residues in the binding sites, movement of specific amino acid residues at certain pH values, distinct amino acid-ligand interactions (side chain donors/acceptors, H-arene bonding, backbone donors/acceptors) and differences in the conformations of each protein-ligand complex. The pKa values obtained from the binding experiment and the results from the molecular simulations served as tools for detecting polar interactions between the PBPs and ligands. The differences found between structures docked with ligand enantiomers reveal the enantioselectivity of the gypsy moth PBPs towards the pheromone and its antipode, as well as towards enantiomers of pheromone analogs with heteroatom substitutions.
authors.affiliation: Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada.
authors.forename: Jurgen T
authors.initials: JT
authors.lastname: Sanes
authors.affiliation: Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada. Electronic address: plettner@sfu.ca.
authors.forename: Erika
authors.initials: E
authors.lastname: Plettner
mesh_terms: D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D003198:Computer Simulation; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D019476:Insect Proteins / Q000737:chemistry*; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009036:Moths / Q000378:metabolism*; D010675:Pheromones / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D012903:Smell; D013237:Stereoisomerism
chemical_list: D002352:Carrier Proteins; D019476:Insect Proteins; D008024:Ligands; D010675:Pheromones; D006639:Histidine
keywords: Gypsy moth; Homology modeling; Ligand interactions; Olfaction; Pheromone-binding protein; pH profile of ligand binding