Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies

Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent worldwide and one of the suggestions to overcome this disease is by using targeted drug delivery. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), a multifunctional protein and virulence factor in pathogenic mi...

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Main Author:	Noh, Muhammad Amirul Asyraf
Format:	Thesis
Language:	English
Published:	2023
Subjects:	RS1-441 Pharmacy and materia medica
Online Access:	http://eprints.usm.my/60460/1/MUHAMMAD%20AMIRUL%20ASYRAF%20BIN%20NOH%20-%20TESIS%20cut.pdf
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spelling	my-usm-ep.604602024-04-29T04:20:09Z Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies 2023-01 Noh, Muhammad Amirul Asyraf RS1-441 Pharmacy and materia medica Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent worldwide and one of the suggestions to overcome this disease is by using targeted drug delivery. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), a multifunctional protein and virulence factor in pathogenic microorganisms is suitable to be the designated drug target as it has been located on the cell surface of Mycobacterium tuberculosis (M. TB) recently. This research is focused on finding the suitable targeting molecules towards GAPDH that can be used for the development of targeted antituberculosis agents. Around 14 molecules with previously reported in vitro and/or in vivo activities against GAPDH or usages as targeting agents were assessed for their binding affinity through molecular docking technique using AutoDock 4.2. Among these 14 molecules, folic acid, NP-014428 and CGP 3466 were discovered to possess the best binding affinity with GAPDH. 13 derivatives of folic acid were then docked against GAPDH. F7 (folic acid N-hydroxysuccinimide ester) and F8 (γ-{[tert-butyl-N-(2-aminoethyl)]carbamate} folic acid) were discovered to possess the most favourable binding affinity among the folic acid derivatives. Consequently, F7 and folic acid were sent to undergo molecular dynamics (MD) simulations with GAPDH using GROMACS 2021.2 alongside NAD (nicotinamide adenine dinucleotide), the natural ligand of GAPDH as positive control agent. Compared to the NAD/GAPDH complex, folic acid/GAPDH complex has the most stable conformation but with the weakest binding affinity whereas F7/GAPDH complex having the most unstable conformation but has the strongest binding affinity. 2023-01 Thesis http://eprints.usm.my/60460/ http://eprints.usm.my/60460/1/MUHAMMAD%20AMIRUL%20ASYRAF%20BIN%20NOH%20-%20TESIS%20cut.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Farmasi
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	RS1-441 Pharmacy and materia medica
spellingShingle	RS1-441 Pharmacy and materia medica Noh, Muhammad Amirul Asyraf Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies
description	Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent worldwide and one of the suggestions to overcome this disease is by using targeted drug delivery. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), a multifunctional protein and virulence factor in pathogenic microorganisms is suitable to be the designated drug target as it has been located on the cell surface of Mycobacterium tuberculosis (M. TB) recently. This research is focused on finding the suitable targeting molecules towards GAPDH that can be used for the development of targeted antituberculosis agents. Around 14 molecules with previously reported in vitro and/or in vivo activities against GAPDH or usages as targeting agents were assessed for their binding affinity through molecular docking technique using AutoDock 4.2. Among these 14 molecules, folic acid, NP-014428 and CGP 3466 were discovered to possess the best binding affinity with GAPDH. 13 derivatives of folic acid were then docked against GAPDH. F7 (folic acid N-hydroxysuccinimide ester) and F8 (γ-{[tert-butyl-N-(2-aminoethyl)]carbamate} folic acid) were discovered to possess the most favourable binding affinity among the folic acid derivatives. Consequently, F7 and folic acid were sent to undergo molecular dynamics (MD) simulations with GAPDH using GROMACS 2021.2 alongside NAD (nicotinamide adenine dinucleotide), the natural ligand of GAPDH as positive control agent. Compared to the NAD/GAPDH complex, folic acid/GAPDH complex has the most stable conformation but with the weakest binding affinity whereas F7/GAPDH complex having the most unstable conformation but has the strongest binding affinity.
format	Thesis
qualification_level	Master's degree
author	Noh, Muhammad Amirul Asyraf
author_facet	Noh, Muhammad Amirul Asyraf
author_sort	Noh, Muhammad Amirul Asyraf
title	Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies
title_short	Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies
title_full	Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies
title_fullStr	Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies
title_full_unstemmed	Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies
title_sort	discovery of new targeting agents against gapdh receptor: in silico and in vitro studies
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Farmasi
publishDate	2023
url	http://eprints.usm.my/60460/1/MUHAMMAD%20AMIRUL%20ASYRAF%20BIN%20NOH%20-%20TESIS%20cut.pdf
_version_	1804888941890895872

Discovery Of New Targeting Agents Against Gapdh Receptor: In Silico And In Vitro Studies

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