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In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein

Background: Andrographolide and its benzylidene derivatives, SRJ09 and SRJ23, potentially bind oncogenic K-Ras to exert anticancer activity. Their molecular interactions with K-Ras oncoproteins that lead to effective biological activity are of major interest. Methods & results: In silico docking...

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Main Authors: Shun, Ying Quah, Tan, Michelle Siying, Kok, Lian Ho, Abd Manan, Nizar, Gorfe, Alemayehu A., Deb, Pran Kishore, Sagineedu, Sreenivasa Rao, Stanslas, Johnson
Format: Article
Language:English
Published: Future Science 2020
Online Access:http://psasir.upm.edu.my/id/eprint/89328/1/NMR.pdf
http://psasir.upm.edu.my/id/eprint/89328/
https://www.future-science.com/doi/10.4155/fmc-2020-0104?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
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spelling my.upm.eprints.893282021-08-19T23:09:28Z http://psasir.upm.edu.my/id/eprint/89328/ In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein Shun, Ying Quah Tan, Michelle Siying Kok, Lian Ho Abd Manan, Nizar Gorfe, Alemayehu A. Deb, Pran Kishore Sagineedu, Sreenivasa Rao Stanslas, Johnson Background: Andrographolide and its benzylidene derivatives, SRJ09 and SRJ23, potentially bind oncogenic K-Ras to exert anticancer activity. Their molecular interactions with K-Ras oncoproteins that lead to effective biological activity are of major interest. Methods & results: In silico docking and molecular dynamics simulation were performed using Glide and Desmond, respectively; while saturation transfer difference NMR was performed using GDP-bound K-RasG12V. SRJ23 was found to bind strongly and selectively to K-RasG12V, by anchoring to a binding pocket (namely p2) principally via hydrogen bond and hydrophobic interactions. The saturation transfer difference NMR analysis revealed the proximity of protons of functional moieties in SRJ23 to K-RasG12V, suggesting positive binding. Conclusion: SRJ23 binds strongly and interacts stably with K-RasG12V to exhibit its inhibitory activity. Future Science 2020 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/89328/1/NMR.pdf Shun, Ying Quah and Tan, Michelle Siying and Kok, Lian Ho and Abd Manan, Nizar and Gorfe, Alemayehu A. and Deb, Pran Kishore and Sagineedu, Sreenivasa Rao and Stanslas, Johnson (2020) In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein. Future Medicinal Chemistry, 12 (18). 1611 - 1631. ISSN 1756-8919; ESSN: 1756-8927 https://www.future-science.com/doi/10.4155/fmc-2020-0104?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed 10.4155/fmc-2020-0104
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Background: Andrographolide and its benzylidene derivatives, SRJ09 and SRJ23, potentially bind oncogenic K-Ras to exert anticancer activity. Their molecular interactions with K-Ras oncoproteins that lead to effective biological activity are of major interest. Methods & results: In silico docking and molecular dynamics simulation were performed using Glide and Desmond, respectively; while saturation transfer difference NMR was performed using GDP-bound K-RasG12V. SRJ23 was found to bind strongly and selectively to K-RasG12V, by anchoring to a binding pocket (namely p2) principally via hydrogen bond and hydrophobic interactions. The saturation transfer difference NMR analysis revealed the proximity of protons of functional moieties in SRJ23 to K-RasG12V, suggesting positive binding. Conclusion: SRJ23 binds strongly and interacts stably with K-RasG12V to exhibit its inhibitory activity.
format Article
author Shun, Ying Quah
Tan, Michelle Siying
Kok, Lian Ho
Abd Manan, Nizar
Gorfe, Alemayehu A.
Deb, Pran Kishore
Sagineedu, Sreenivasa Rao
Stanslas, Johnson
spellingShingle Shun, Ying Quah
Tan, Michelle Siying
Kok, Lian Ho
Abd Manan, Nizar
Gorfe, Alemayehu A.
Deb, Pran Kishore
Sagineedu, Sreenivasa Rao
Stanslas, Johnson
In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein
author_facet Shun, Ying Quah
Tan, Michelle Siying
Kok, Lian Ho
Abd Manan, Nizar
Gorfe, Alemayehu A.
Deb, Pran Kishore
Sagineedu, Sreenivasa Rao
Stanslas, Johnson
author_sort Shun, Ying Quah
title In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein
title_short In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein
title_full In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein
title_fullStr In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein
title_full_unstemmed In silico and saturation transfer difference NMR approaches to unravel the binding mode of an andrographolide derivative to K-Ras oncoprotein
title_sort in silico and saturation transfer difference nmr approaches to unravel the binding mode of an andrographolide derivative to k-ras oncoprotein
publisher Future Science
publishDate 2020
url http://psasir.upm.edu.my/id/eprint/89328/1/NMR.pdf
http://psasir.upm.edu.my/id/eprint/89328/
https://www.future-science.com/doi/10.4155/fmc-2020-0104?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
_version_ 1709669006270529536
score 13.251813

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