In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking

Glioblastoma multiforme (GBM) is a high-grade brain tumor of which the survival patients remain poor. Tousled-like kinase 1 (TLK1), a serine-threonine kinase, was identified to be overexpressed in cancers such as GBM. TLK1 plays an important role in controlling survival pathways. To date, there is n...

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Main Authors:	Kamariah Ibrahim, Abubakar Danjuma Abdullahi, Nor Azian Abdul Murad, Roslan Harun, Rahman Jamal
Format:	Article
Language:	English
Published:	Pusat Perubatan Universiti Kebangsaan Malaysia 2018
Online Access:	http://journalarticle.ukm.my/13245/ http://journalarticle.ukm.my/13245/ http://journalarticle.ukm.my/13245/1/38-134-1-PB.pdf

id	ukm-13245
recordtype	eprints
spelling	ukm-132452019-08-02T04:07:44Z http://journalarticle.ukm.my/13245/ In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking Kamariah Ibrahim, Abubakar Danjuma Abdullahi, Nor Azian Abdul Murad, Roslan Harun, Rahman Jamal, Glioblastoma multiforme (GBM) is a high-grade brain tumor of which the survival patients remain poor. Tousled-like kinase 1 (TLK1), a serine-threonine kinase, was identified to be overexpressed in cancers such as GBM. TLK1 plays an important role in controlling survival pathways. To date, there is no structure available for TLK1 as well as its inhibitors. We aimed to create a homology model of TLK1 and to identify suitable molecular inhibitors that are likely to bind and inhibit TLK1 activity via in silico high-throughput virtual screening (HTVS) protein-ligand docking. The 3D homology models of TLK1 were derived from various servers. All models were evaluated using Swiss Model QMEAN server. Validation was performed using multiple tools. Energy minimization was performed using YASARA. Subsequently, HTVS was performed using Molegro Virtual Docker 6.0 and ligands derived from ligand.info database. Drug-like molecules were filtered using ADME-Tox filtering program. Best homology model was obtained from the Aurora B kinase (PDB ID:4B8M) derived from Xenopus levias structure that share sequence similarity with human TLK1. Two compounds were identified from HTVS to be the potential inhibitors as it did not violate the Lipinski rule of five and the CNS-based filter as a potential drug-like molecule for GBM. Pusat Perubatan Universiti Kebangsaan Malaysia 2018 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/13245/1/38-134-1-PB.pdf Kamariah Ibrahim, and Abubakar Danjuma Abdullahi, and Nor Azian Abdul Murad, and Roslan Harun, and Rahman Jamal, (2018) In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking. Asia-Pacific Journal of Molecular Medicine, 8 (1). pp. 1-14. ISSN 2232-0326 http://spaj.ukm.my/apjmm/index.php/apjmm/issue/view/18
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Kebangasaan Malaysia
building	UKM Institutional Repository
collection	Online Access
language	English
description	Glioblastoma multiforme (GBM) is a high-grade brain tumor of which the survival patients remain poor. Tousled-like kinase 1 (TLK1), a serine-threonine kinase, was identified to be overexpressed in cancers such as GBM. TLK1 plays an important role in controlling survival pathways. To date, there is no structure available for TLK1 as well as its inhibitors. We aimed to create a homology model of TLK1 and to identify suitable molecular inhibitors that are likely to bind and inhibit TLK1 activity via in silico high-throughput virtual screening (HTVS) protein-ligand docking. The 3D homology models of TLK1 were derived from various servers. All models were evaluated using Swiss Model QMEAN server. Validation was performed using multiple tools. Energy minimization was performed using YASARA. Subsequently, HTVS was performed using Molegro Virtual Docker 6.0 and ligands derived from ligand.info database. Drug-like molecules were filtered using ADME-Tox filtering program. Best homology model was obtained from the Aurora B kinase (PDB ID:4B8M) derived from Xenopus levias structure that share sequence similarity with human TLK1. Two compounds were identified from HTVS to be the potential inhibitors as it did not violate the Lipinski rule of five and the CNS-based filter as a potential drug-like molecule for GBM.
format	Article
author	Kamariah Ibrahim, Abubakar Danjuma Abdullahi, Nor Azian Abdul Murad, Roslan Harun, Rahman Jamal,
spellingShingle	Kamariah Ibrahim, Abubakar Danjuma Abdullahi, Nor Azian Abdul Murad, Roslan Harun, Rahman Jamal, In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking
author_facet	Kamariah Ibrahim, Abubakar Danjuma Abdullahi, Nor Azian Abdul Murad, Roslan Harun, Rahman Jamal,
author_sort	Kamariah Ibrahim,
title	In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking
title_short	In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking
title_full	In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking
title_fullStr	In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking
title_full_unstemmed	In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking
title_sort	in silico homology modelling and identification of tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking
publisher	Pusat Perubatan Universiti Kebangsaan Malaysia
publishDate	2018
url	http://journalarticle.ukm.my/13245/ http://journalarticle.ukm.my/13245/ http://journalarticle.ukm.my/13245/1/38-134-1-PB.pdf
first_indexed	2023-09-18T20:04:25Z
last_indexed	2023-09-18T20:04:25Z
_version_	1777407062991437824

In silico homology modelling and identification of Tousled-like kinase 1 inhibitors for glioblastoma therapy via high throughput virtual screening protein-ligand docking

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