Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches

Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches

The human hexokinase II (HK2) has been suggested as a potential therapeutic target for the development of drugs against dengue virus (DENV) infection. In this paper, compounds with potential HK2 inhibitory activity have been identified using ligandbased and structure-based virtual screening appro...

Full description

Bibliographic Details
Main Authors: Ahmad Fuad, Fazia Adyani, Abdul Hamid, Azzmer Azzar, Saadun, Rafidah
Format: Conference or Workshop Item
Language:English
English
English
Published: UKM 2017
Subjects:
QD Chemistry
Online Access:http://irep.iium.edu.my/59797/
http://irep.iium.edu.my/59797/1/ARCSB%20Rafidah%20et%20al.%202017.pdf
http://irep.iium.edu.my/59797/7/Copyright%20page%20ARCSB2017%20Book%20v4-1.pdf
http://irep.iium.edu.my/59797/8/List%20of%20title.pdf
id iium-59797
recordtype eprints
spelling iium-597972017-12-05T08:24:31Z http://irep.iium.edu.my/59797/ Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches Ahmad Fuad, Fazia Adyani Abdul Hamid, Azzmer Azzar Saadun, Rafidah QD Chemistry The human hexokinase II (HK2) has been suggested as a potential therapeutic target for the development of drugs against dengue virus (DENV) infection. In this paper, compounds with potential HK2 inhibitory activity have been identified using ligandbased and structure-based virtual screening approaches. Ligand-based drug design was performed by using Ultra-Fast Shape Recognition with Atom Types (UFSRAT) and Ultrafast Shape Recognition with CREDO Atom Types (USRCAT) programmes by utilising 2-Deoxyglucose (2-DG) as the query molecule, which is a known HK2 inhibitor. The molecules identified from the programmes showed great similarity to 2-DG with scores ranged from 0.78-0.85 and 0.88-0.97 for UFSRAT and USRCAT, respectively. The analogues were docked against the crystal structure of HK2 (PDB ID: 2NZT) in complex with alpha-D-glucose (GLC) and beta-D-glucose-6-phosphate (BG6) by using AutoDock Vina programme, on both A and B chains where the active sites were located. The docking hits for molecules from UFSRAT showed binding energies ranged from -7.1 to -4.8 kcal/mol when docked on chain A, while the hits for chain B showed scores ranged from -6.7 to -4.8 kcal/mol. On the other hand, the binding energies for molecules from USRCAT when docked on both A and B chains were similar, which ranged from -7.0 to - 5.2 kcal/mol. The hits bind firmly at the cavities, where both GLC and BG6 were oriented towards the active sites of HK2. Taken together, this study has successfully discovered compounds which have potentials as potent inhibitors of HK2, thus pave the path towards the development of dengue therapeutics. UKM 2017-11-20 Conference or Workshop Item PeerReviewed application/pdf en http://irep.iium.edu.my/59797/1/ARCSB%20Rafidah%20et%20al.%202017.pdf application/pdf en http://irep.iium.edu.my/59797/7/Copyright%20page%20ARCSB2017%20Book%20v4-1.pdf application/pdf en http://irep.iium.edu.my/59797/8/List%20of%20title.pdf Ahmad Fuad, Fazia Adyani and Abdul Hamid, Azzmer Azzar and Saadun, Rafidah (2017) Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches. In: 4th Asian Regional Conference on Systems Biology, 20-22 Nov 2017, Putrajaya.
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
English
English
topic QD Chemistry
spellingShingle QD Chemistry
Ahmad Fuad, Fazia Adyani
Abdul Hamid, Azzmer Azzar
Saadun, Rafidah
Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches
description The human hexokinase II (HK2) has been suggested as a potential therapeutic target for the development of drugs against dengue virus (DENV) infection. In this paper, compounds with potential HK2 inhibitory activity have been identified using ligandbased and structure-based virtual screening approaches. Ligand-based drug design was performed by using Ultra-Fast Shape Recognition with Atom Types (UFSRAT) and Ultrafast Shape Recognition with CREDO Atom Types (USRCAT) programmes by utilising 2-Deoxyglucose (2-DG) as the query molecule, which is a known HK2 inhibitor. The molecules identified from the programmes showed great similarity to 2-DG with scores ranged from 0.78-0.85 and 0.88-0.97 for UFSRAT and USRCAT, respectively. The analogues were docked against the crystal structure of HK2 (PDB ID: 2NZT) in complex with alpha-D-glucose (GLC) and beta-D-glucose-6-phosphate (BG6) by using AutoDock Vina programme, on both A and B chains where the active sites were located. The docking hits for molecules from UFSRAT showed binding energies ranged from -7.1 to -4.8 kcal/mol when docked on chain A, while the hits for chain B showed scores ranged from -6.7 to -4.8 kcal/mol. On the other hand, the binding energies for molecules from USRCAT when docked on both A and B chains were similar, which ranged from -7.0 to - 5.2 kcal/mol. The hits bind firmly at the cavities, where both GLC and BG6 were oriented towards the active sites of HK2. Taken together, this study has successfully discovered compounds which have potentials as potent inhibitors of HK2, thus pave the path towards the development of dengue therapeutics.
format Conference or Workshop Item
author Ahmad Fuad, Fazia Adyani
Abdul Hamid, Azzmer Azzar
Saadun, Rafidah
author_facet Ahmad Fuad, Fazia Adyani
Abdul Hamid, Azzmer Azzar
Saadun, Rafidah
author_sort Ahmad Fuad, Fazia Adyani
title Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches
title_short Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches
title_full Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches
title_fullStr Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches
title_full_unstemmed Identifying potential inhibitors of human hexokinase II for the development of anti-dengue therapeutics via virtual screening approaches
title_sort identifying potential inhibitors of human hexokinase ii for the development of anti-dengue therapeutics via virtual screening approaches
publisher UKM
publishDate 2017
url http://irep.iium.edu.my/59797/
http://irep.iium.edu.my/59797/1/ARCSB%20Rafidah%20et%20al.%202017.pdf
http://irep.iium.edu.my/59797/7/Copyright%20page%20ARCSB2017%20Book%20v4-1.pdf
http://irep.iium.edu.my/59797/8/List%20of%20title.pdf
first_indexed 2023-09-18T21:24:44Z
last_indexed 2023-09-18T21:24:44Z
_version_ 1777412116009975808

Similar Items