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dc.contributor.authorAl-Obaidi, Anas
dc.contributor.authorElmezayen, Ammar D
dc.contributor.authorYelekçi, Kemal
dc.date.accessioned2020-07-16T07:51:47Z
dc.date.available2020-07-16T07:51:47Z
dc.date.issued2020
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.urihttps://doi.org/10.1080/07391102.2020.1774417en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/3042
dc.description.abstractGamma-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5 '-phosphate (PLP)-dependent enzyme which degrades gamma-aminobutyric (GABA) in the brain. GABA is an important inhibitory neurotransmitter that plays important neurological roles in the brain. Therefore, GABA-AT is an important drug target which regulates the GABA level. Novel and potent drug development to inhibit GABA-AT is still very challenging task. In this study, we aimed to devise novel and potent inhibitors against GABA-AT using computer-aided drug design (CADD) tools. However, the human GABA-AT crystal structure is not available yet, and we built the 3D structure of human GABA-AT based on the crystal structure of pig's liver (Sus Scrofa) enzyme as a template. The generated model was validated with numerous tools such as ProSA and PROCHECK. A set of selected well-known inhibitors have been tested against the modeled GABA-AT. Molecular docking studies have been accomplished via application of Genetic Optimization for Ligand Docking (GOLD), Vina and Autodock 4.2 software to search for potent inhibitors. The best two candidate inhibitors have been computationally examined for absorption, distribution, metabolism, elimination and toxicity descriptors (ADMET) and Lipinski's rule of 5. Lastly, molecular dynamics (MD) simulations were carried out to inspect the ligands' binding mode and stability of the active site of human GABA-AT over time. The top ranked ligands exhibited reliable stability throughout the MD simulation. The selected compounds are promising candidates and might be tested experimentally for the inhibition of human GABA-AT enzyme. Communicated by Ramaswamy H. Sarmaen_US
dc.language.isoEnglishen_US
dc.publisherTaylor & Francis Incen_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectGABA-ATen_US
dc.subjectHomology modeling of human GABA-ATen_US
dc.subjectVirtual screening;en_US
dc.subjectMolecular dynamics simulationen_US
dc.subjectPotent GABA-AT inhibitorsen_US
dc.titleHomology modeling of human GABA-AT and devise some novel and potent inhibitors via computer-aided drug design techniquesen_US
dc.typeArticleen_US
dc.relation.journalJournal of Biomolecular Structure & Dynamicsen_US
dc.identifier.wosWOS:000544272600001en_US
dc.identifier.doi10.1080/07391102.2020.1774417en_US
dc.contributor.khasauthorAl-Obaidi, Anasen_US
dc.contributor.khasauthorElmezayen, Ammar D.en_US
dc.contributor.khasauthorYelekçi, Kemalen_US


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