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A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods
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 ho...
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| Format: | Thesis |
| Language: | English |
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Department of Chemistry
2021
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| _version_ | 1867613629643227136 |
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| access_status_str | Open Access |
| author | Abdulganiyyu, Ibrahim A |
| author2 | Jackson, Graham E |
| author_browse | Abdulganiyyu, Ibrahim A Jackson, Graham E |
| author_facet | Jackson, Graham E Abdulganiyyu, Ibrahim A |
| author_sort | Abdulganiyyu, Ibrahim A |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/33621 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:39:11.560Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Department of Chemistry |
| publisherStr | Department of Chemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/33621 A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods Abdulganiyyu, Ibrahim A Jackson, Graham E Marco, Heather G Adipokinetic hormones Adipokinetic hormone-receptor Beta2-adrenergic receptors Docking G-protein coupled receptors GROMACS Homology modelling Molecular dynamics simulation 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. 2021-07-13T10:57:52Z 2021-07-13T10:57:52Z 2021 2021-07-13T10:32:53Z Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/33621 eng application/pdf Department of Chemistry Faculty of Science |
| spellingShingle | Adipokinetic hormones Adipokinetic hormone-receptor Beta2-adrenergic receptors Docking G-protein coupled receptors GROMACS Homology modelling Molecular dynamics simulation Abdulganiyyu, Ibrahim A A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods |
| thesis_degree_str | Doctoral |
| title | A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods |
| title_full | A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods |
| title_fullStr | A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods |
| title_full_unstemmed | A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods |
| title_short | A single AKH neuropeptide activating three different fly AKH-receptors: an insecticide study via computational methods |
| title_sort | single akh neuropeptide activating three different fly akh receptors an insecticide study via computational methods |
| topic | Adipokinetic hormones Adipokinetic hormone-receptor Beta2-adrenergic receptors Docking G-protein coupled receptors GROMACS Homology modelling Molecular dynamics simulation |
| url | http://hdl.handle.net/11427/33621 |
| work_keys_str_mv | AT abdulganiyyuibrahima asingleakhneuropeptideactivatingthreedifferentflyakhreceptorsaninsecticidestudyviacomputationalmethods AT abdulganiyyuibrahima singleakhneuropeptideactivatingthreedifferentflyakhreceptorsaninsecticidestudyviacomputationalmethods |