In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase

The frightening development of antimicrobial resistant bacteria (AMR) poses an explicit threat to life. This threat is still in an upward curve due to the indiscriminate and overuse of antimicrobials. Therefore, it is essential for the scientific community to keep pace with this development and sear...

Full description

Saved in:

Bibliographic Details
Main Author:	Albaskeni, Abdulrhman Mahmoud
Format:	Thesis
Language:	English
Published:	2021
Subjects:	QR75-99.5 Bacteria
Online Access:	http://eprints.usm.my/57901/1/Albaskeni-24%20pages.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-usm-ep.57901
record_format	uketd_dc
spelling	my-usm-ep.579012023-04-12T01:10:01Z In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase 2021-10 Albaskeni, Abdulrhman Mahmoud QR75-99.5 Bacteria The frightening development of antimicrobial resistant bacteria (AMR) poses an explicit threat to life. This threat is still in an upward curve due to the indiscriminate and overuse of antimicrobials. Therefore, it is essential for the scientific community to keep pace with this development and search for alternative solutions to stop AMR. Choline kinase (ChoK) is considered as one of the new targets for inhibition to combat AMR. In Gram-positive bacteria, choline kinase is responsible for the synthesis of phosphorylcholine, a precursor of lipoteichoic acid and cell wall teichoic acid. In Gram-negative bacteria, phosphorylcholine is incorporated into the membrane lipopolysaccharides. Human choline kinase inhibitor (ChoKIs) has already been tested on Streptococcus pneumoniae with encouraging results by causing degradation of bacterial cell wall. In this study, in silico bioinformatics analysis of putative Klebsiella pneumoniae choline kinase (KpChoK) was performed to search for the best conditions for the production of recombinant KpChoK in the future. Evaluation of ChoKIs as the potential inhibitors of KpChoK by structural modeling and molecular docking approaches were also carried out. The prediction of protein solubility revealed that the solubility of KpChoK was lower than that of the average soluble Escherichia coli proteins. Molecular docking of KpChoK model structures with hemicholinium-3 (HC-3), a well-established ChoKI, showed a suitable binding mode within the choline binding pocket, indicating a promising competitive inhibition by HC-3. These results of molecular docking thus indicate the promising application of ChoKIs to combat antimicrobial resistance. Therefore, this study paved the way towards successful overexpression of soluble KpChoK to be tested with currently available ChoKIs and reveals the potential of these compounds as novel anti-K. pneumoniae agents. Although the KpChoK was predicted to have low solubility in E. coli expression system, several methods have been discussed to improve the solubility. In the future, nanoparticles can also be used to enhance the activity of ChoKIs by acting as a drug delivery system. 2021-10 Thesis http://eprints.usm.my/57901/ http://eprints.usm.my/57901/1/Albaskeni-24%20pages.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Kesihatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	QR75-99.5 Bacteria
spellingShingle	QR75-99.5 Bacteria Albaskeni, Abdulrhman Mahmoud In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase
description	The frightening development of antimicrobial resistant bacteria (AMR) poses an explicit threat to life. This threat is still in an upward curve due to the indiscriminate and overuse of antimicrobials. Therefore, it is essential for the scientific community to keep pace with this development and search for alternative solutions to stop AMR. Choline kinase (ChoK) is considered as one of the new targets for inhibition to combat AMR. In Gram-positive bacteria, choline kinase is responsible for the synthesis of phosphorylcholine, a precursor of lipoteichoic acid and cell wall teichoic acid. In Gram-negative bacteria, phosphorylcholine is incorporated into the membrane lipopolysaccharides. Human choline kinase inhibitor (ChoKIs) has already been tested on Streptococcus pneumoniae with encouraging results by causing degradation of bacterial cell wall. In this study, in silico bioinformatics analysis of putative Klebsiella pneumoniae choline kinase (KpChoK) was performed to search for the best conditions for the production of recombinant KpChoK in the future. Evaluation of ChoKIs as the potential inhibitors of KpChoK by structural modeling and molecular docking approaches were also carried out. The prediction of protein solubility revealed that the solubility of KpChoK was lower than that of the average soluble Escherichia coli proteins. Molecular docking of KpChoK model structures with hemicholinium-3 (HC-3), a well-established ChoKI, showed a suitable binding mode within the choline binding pocket, indicating a promising competitive inhibition by HC-3. These results of molecular docking thus indicate the promising application of ChoKIs to combat antimicrobial resistance. Therefore, this study paved the way towards successful overexpression of soluble KpChoK to be tested with currently available ChoKIs and reveals the potential of these compounds as novel anti-K. pneumoniae agents. Although the KpChoK was predicted to have low solubility in E. coli expression system, several methods have been discussed to improve the solubility. In the future, nanoparticles can also be used to enhance the activity of ChoKIs by acting as a drug delivery system.
format	Thesis
qualification_level	Master's degree
author	Albaskeni, Abdulrhman Mahmoud
author_facet	Albaskeni, Abdulrhman Mahmoud
author_sort	Albaskeni, Abdulrhman Mahmoud
title	In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase
title_short	In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase
title_full	In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase
title_fullStr	In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase
title_full_unstemmed	In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase
title_sort	in silico analysis, structural modelling and molecular docking of putative klebsiella pneumoniae choline kinase
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Kesihatan
publishDate	2021
url	http://eprints.usm.my/57901/1/Albaskeni-24%20pages.pdf
_version_	1776101212230254592

In silico analysis, structural modelling and molecular docking of putative Klebsiella pneumoniae choline kinase

Similar Items