A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods
| dc.contributor.advisor | Jackson, Graham E | |
| dc.contributor.advisor | Marco, Heather G | |
| dc.contributor.author | Abdulganiyyu, Ibrahim A | |
| dc.date.accessioned | 2021-07-13T10:57:52Z | |
| dc.date.available | 2021-07-13T10:57:52Z | |
| dc.date.issued | 2021 | |
| dc.date.updated | 2021-07-13T10:32:53Z | |
| dc.description.abstract | Flies are a widely distributed pest insect that poses a significant threat to food security. Flight is essential for the dispersal of the adult flies to find new food sources and ideal breeding spots. The supply of metabolic fuel to power the flight muscles of insects is regulated by adipokinetic hormones (AKHs). The fruit fly, Drosophila melanogaster, the flesh fly, Sarcophaga crassipalpis, and the oriental fruit fly, Bactrocera dorsalis all have the same AKH that is present in the blowfly, Phormia terraenovae; this AKH has the code-name Phote-HrTH. Binding of the AKH to the extracellular binding site of a G protein-coupled receptor causes its activation. In this thesis, the structure of Phote-HrTH in SDS micelle solution was determined using NMR restrained molecular dynamics. The peptide was found to bind to the micelle and be reasonably rigid, with an S 2 order parameter of 0.96. The translated protein sequence of the AKH receptor from the fruit fly, Drosophila melanogaster, the flesh fly, Sarcophaga crassipalpis, and the oriental fruit fly, Bactrocera dorsalis were used to construct two models for each receptor: Drome-AKHR, Sarcr-AKHR, and Bacdo-AKHR. It is proposed that these two models represent the active and inactive state of the receptor. The models based on the crystal structure of the β-2 adrenergic receptor were found to bind Phote-HrTH with a predicted binding free energy of –107 kJ mol–1 for Drome-AKHR, –102 kJ mol–1 for Sarcr-AKHR and –102 kJ mol–1 for Bacdo-AKHR. Under molecular dynamics simulation, in a POPC membrane, the β-2AR receptor-like complexes transformed to rhodopsin-like. The identification and characterisation of the ligand-binding site of each receptor provide novel information on ligand-receptor interactions, which could lead to the development of species-specific control substances to use discriminately against these pest flies. | |
| dc.identifier.apacitation | Abdulganiyyu, I. A. (2021). <i>A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods</i>. (). ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/33621 | en_ZA |
| dc.identifier.chicagocitation | Abdulganiyyu, Ibrahim A. <i>"A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods."</i> ., ,Faculty of Science ,Department of Chemistry, 2021. http://hdl.handle.net/11427/33621 | en_ZA |
| dc.identifier.citation | Abdulganiyyu, I.A. 2021. A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods. . ,Faculty of Science ,Department of Chemistry. http://hdl.handle.net/11427/33621 | en_ZA |
| dc.identifier.ris | TY - Doctoral Thesis AU - Abdulganiyyu, Ibrahim A AB - Flies are a widely distributed pest insect that poses a significant threat to food security. Flight is essential for the dispersal of the adult flies to find new food sources and ideal breeding spots. The supply of metabolic fuel to power the flight muscles of insects is regulated by adipokinetic hormones (AKHs). The fruit fly, Drosophila melanogaster, the flesh fly, Sarcophaga crassipalpis, and the oriental fruit fly, Bactrocera dorsalis all have the same AKH that is present in the blowfly, Phormia terraenovae; this AKH has the code-name Phote-HrTH. Binding of the AKH to the extracellular binding site of a G protein-coupled receptor causes its activation. In this thesis, the structure of Phote-HrTH in SDS micelle solution was determined using NMR restrained molecular dynamics. The peptide was found to bind to the micelle and be reasonably rigid, with an S 2 order parameter of 0.96. The translated protein sequence of the AKH receptor from the fruit fly, Drosophila melanogaster, the flesh fly, Sarcophaga crassipalpis, and the oriental fruit fly, Bactrocera dorsalis were used to construct two models for each receptor: Drome-AKHR, Sarcr-AKHR, and Bacdo-AKHR. It is proposed that these two models represent the active and inactive state of the receptor. The models based on the crystal structure of the β-2 adrenergic receptor were found to bind Phote-HrTH with a predicted binding free energy of –107 kJ mol–1 for Drome-AKHR, –102 kJ mol–1 for Sarcr-AKHR and –102 kJ mol–1 for Bacdo-AKHR. Under molecular dynamics simulation, in a POPC membrane, the β-2AR receptor-like complexes transformed to rhodopsin-like. The identification and characterisation of the ligand-binding site of each receptor provide novel information on ligand-receptor interactions, which could lead to the development of species-specific control substances to use discriminately against these pest flies. DA - 2021_ DB - OpenUCT DP - University of Cape Town KW - Adipokinetic hormones KW - Adipokinetic hormone-receptor KW - Beta2-adrenergic receptors KW - Docking KW - G-protein KW - coupled receptors KW - GROMACS KW - Homology modelling KW - Molecular dynamics simulation LK - https://open.uct.ac.za PY - 2021 T1 - A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods TI - A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods UR - http://hdl.handle.net/11427/33621 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/33621 | |
| dc.identifier.vancouvercitation | Abdulganiyyu IA. A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods. []. ,Faculty of Science ,Department of Chemistry, 2021 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/33621 | en_ZA |
| dc.language.rfc3066 | eng | |
| dc.publisher.department | Department of Chemistry | |
| dc.publisher.faculty | Faculty of Science | |
| dc.subject | Adipokinetic hormones | |
| dc.subject | Adipokinetic hormone-receptor | |
| dc.subject | Beta2-adrenergic receptors | |
| dc.subject | Docking | |
| dc.subject | G-protein | |
| dc.subject | coupled receptors | |
| dc.subject | GROMACS | |
| dc.subject | Homology modelling | |
| dc.subject | Molecular dynamics simulation | |
| dc.title | A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods | |
| dc.type | Doctoral Thesis | |
| dc.type.qualificationlevel | Doctoral | |
| dc.type.qualificationlevel | PhD |