title: Homology modeling and molecular docking studies of Drosophila and Aedes sex peptide receptors.
abstract: The Drosophila melanogaster sex peptide receptor (DrmSPR), which is a G protein-coupled receptor (GPCR), is known as the specific receptor for sex peptide (SP). It is responsible for the reproductive behavior in the Drosophila model system; in particular, it is involved in the post-mating responses such as the increase in egg-laying ability and decrease in receptivity in females. In a previous study, we discovered a small molecule agonist of DrmSPR for the first time, which could not, however, activate Aedes aegypti SPR (AedesSPR). To investigate the binding mechanism of the small molecule agonist of DrmSPR, the ensemble structures of low-lying packing structures of DrmSPR and AedesSPR were assembled using the GEnSeMBLE (GPCR Ensemble of Structures in Membrane BiLayer Environment) method. The generated homology models exhibited the typical pattern of inter-helical interactions of the class A GPCRs. The docking experiments of the small molecule agonist suggest that Tyr(5.35) and Phe(2.67) residues may be involved in a hydrophobic interaction and that Ser(3.25) forms a hydrogen bond with the agonist. Additionally, we found that the docking results were consistent with the experimental data of the reference compounds with variable agonistic activities. Moreover, a potential distinction of the putative binding sites in two GPCR models of DrmSPR and AedesSPR, which was determined in this study, can explain the selective action of the agonist for DrmSPR but not for AedesSPR.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Materials and Process Simulation Center (MC139-74), California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, United States.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Materials and Process Simulation Center (MC139-74), California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, United States. Electronic address: wag@wag.caltech.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Goddard
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea. Electronic address: yongchul@gist.ac.kr.
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000330:Aedes / Q000737:chemistry*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics; D004331:Drosophila melanogaster / Q000737:chemistry; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D018000:Receptors, Peptide / Q000737:chemistry* / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D018000:Receptors, Peptide; C526291:sex peptide receptor, Drosophila
keywords: BiHelix/SuperBiHelix; Binding site prediction; Docking; Drosophila sex peptide receptor; G protein-coupled receptor; GEnSeMBLE; GPCR modeling; Pyrazolodiazepine