Identification of Selective Novel Hits against Plasmodium falciparum Prolyl tRNA Synthetase Active Site and a Predicted Allosteric Site Using in silico Approaches:

Nyamai, Dorothy W; Tastan Bishop, Özlem

Title: Identification of Selective Novel Hits against Plasmodium falciparum Prolyl tRNA Synthetase Active Site and a Predicted Allosteric Site Using in silico Approaches:
Creator: Nyamai, Dorothy W
Creator: Tastan Bishop, Özlem
Date Issued: 2020
Date: 2020
Type: text
Type: article
Identifier: http://hdl.handle.net/10962/149229
Identifier: vital:38817
Identifier: https://doi.org/10.3390/ijms21113803
Description: Recently, there has been increased interest in aminoacyl tRNA synthetases (aaRSs) as potential malarial drug targets. These enzymes play a key role in protein translation by the addition of amino acids to their cognate tRNA. The aaRSs are present in all Plasmodium life cycle stages, and thus present an attractive malarial drug target. Prolyl tRNA synthetase is a class II aaRS that functions in charging tRNA with proline. Various inhibitors against Plasmodium falciparum ProRS (PfProRS) active site have been designed. However, none have gone through clinical trials as they have been found to be highly toxic to human cells. Recently, a possible allosteric site was reported in PfProRS with two possible allosteric modulators: glyburide and TCMDC-124506. In this study, we sought to identify novel selective inhibitors targeting PfProRS active site and possible novel allosteric modulators of this enzyme. To achieve this, virtual screening of South African natural compounds against PfProRS and the human homologue was carried out using AutoDock Vina. The modulation of protein motions by ligand binding was studied by molecular dynamics (MD) using the GROningen MAchine for Chemical Simulations (GROMACS) tool. To further analyse the protein global motions and energetic changes upon ligand binding, principal component analysis (PCA), and free energy landscape (FEL) calculations were performed.
Format: 34 pages
Format: pdf
Language: English
Relation: International Journal of Molecular Sciences
Relation: Nyamai, D.W. and Tastan Bishop, Ö., 2020. Identification of Selective Novel Hits against Plasmodium falciparum Prolyl tRNA Synthetase Active Site and a Predicted Allosteric Site Using in silico Approaches. International Journal of Molecular Sciences, 21(11), p.3803.
Relation: International Journal of Molecular Sciences volume 21 number 11 p.3808 May 2020 1422-0067
Rights: Publisher
Rights: Use of this resource is governed by the terms and conditions of the MDPI Open Access Statement (https://www.int-res.com/journals/terms-of-use/)

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RU Research Unit in Bioinformatics (RUBi)

Tastan Bishop, Ozlem (Prof)

SDG 03. Good Health and Well-Being

RU Department of Biochemistry, Microbiology and Bioinformatics

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