Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme

Abstract Density functional theory method combined with docking and molecular dynamics simulations are used to understand the interaction of carmustine with human glutathione reductase enzyme. The active site of the enzyme is evaluated by docking simulation is used for molecular dynamics simulation...

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Autores principales:	Saheen Shehnaz Begum, Dharitri Das, Nand Kishor Gour, Ramesh Chandra Deka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f57e35290854630858c98838df437bf
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spelling	oai:doaj.org-article:7f57e35290854630858c98838df437bf2021-12-02T15:53:46ZComputational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme10.1038/s41598-021-84006-12045-2322https://doaj.org/article/7f57e35290854630858c98838df437bf2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84006-1https://doaj.org/toc/2045-2322Abstract Density functional theory method combined with docking and molecular dynamics simulations are used to understand the interaction of carmustine with human glutathione reductase enzyme. The active site of the enzyme is evaluated by docking simulation is used for molecular dynamics simulation to deliver the carmustine molecule by (5,5) single walled carbon nanotube (SWCNT). Our model of carmustine in the active site of GR gives a negative binding energy that is further refined by QM/MM study in gas phase and solvent phase to confirm the stability of the drug molecule inside the active site. Once released from SWCNT, carmustine forms multiple polar and non-polar hydrogen bonding interactions with Tyr180, Phe209, Lys318, Ala319, Leu320, Leu321, Ile350, Thr352 and Val354 in the range of 2–4 Å. The SWCNT vehicle itself is held fix at its place due to multiple pi-pi stacking, pi-amide, pi-sigma interactions with the neighboring residues. These interactions in the range of 3–5 Å are crucial in holding the nanotube outside the drug binding region, hence, making an effective delivery. This study can be extended to envisage the potential applications of computational studies in the modification of known drugs to find newer targets and designing new and improved controlled drug delivery systems.Saheen Shehnaz BegumDharitri DasNand Kishor GourRamesh Chandra DekaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saheen Shehnaz Begum Dharitri Das Nand Kishor Gour Ramesh Chandra Deka Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
description	Abstract Density functional theory method combined with docking and molecular dynamics simulations are used to understand the interaction of carmustine with human glutathione reductase enzyme. The active site of the enzyme is evaluated by docking simulation is used for molecular dynamics simulation to deliver the carmustine molecule by (5,5) single walled carbon nanotube (SWCNT). Our model of carmustine in the active site of GR gives a negative binding energy that is further refined by QM/MM study in gas phase and solvent phase to confirm the stability of the drug molecule inside the active site. Once released from SWCNT, carmustine forms multiple polar and non-polar hydrogen bonding interactions with Tyr180, Phe209, Lys318, Ala319, Leu320, Leu321, Ile350, Thr352 and Val354 in the range of 2–4 Å. The SWCNT vehicle itself is held fix at its place due to multiple pi-pi stacking, pi-amide, pi-sigma interactions with the neighboring residues. These interactions in the range of 3–5 Å are crucial in holding the nanotube outside the drug binding region, hence, making an effective delivery. This study can be extended to envisage the potential applications of computational studies in the modification of known drugs to find newer targets and designing new and improved controlled drug delivery systems.
format	article
author	Saheen Shehnaz Begum Dharitri Das Nand Kishor Gour Ramesh Chandra Deka
author_facet	Saheen Shehnaz Begum Dharitri Das Nand Kishor Gour Ramesh Chandra Deka
author_sort	Saheen Shehnaz Begum
title	Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
title_short	Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
title_full	Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
title_fullStr	Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
title_full_unstemmed	Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
title_sort	computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7f57e35290854630858c98838df437bf
work_keys_str_mv	AT saheenshehnazbegum computationalmodellingofnanotubedeliveryofanticancerdrugintoglutathionereductaseenzyme AT dharitridas computationalmodellingofnanotubedeliveryofanticancerdrugintoglutathionereductaseenzyme AT nandkishorgour computationalmodellingofnanotubedeliveryofanticancerdrugintoglutathionereductaseenzyme AT rameshchandradeka computationalmodellingofnanotubedeliveryofanticancerdrugintoglutathionereductaseenzyme
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Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme

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