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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Future Science
2020
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| Online Access: | http://psasir.upm.edu.my/id/eprint/89328/1/NMR.pdf |
| _version_ | 1825936661672886272 |
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| author | Shun, Ying Quah Tan, Michelle Siying Kok, Lian Ho Abd Manan, Nizar Gorfe, Alemayehu A. Deb, Pran Kishore Sagineedu, Sreenivasa Rao Stanslas, Johnson |
| 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 |
| collection | UPM |
| 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. |
| first_indexed | 2024-03-06T10:47:41Z |
| format | Article |
| id | upm.eprints-89328 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T10:47:41Z |
| publishDate | 2020 |
| publisher | Future Science |
| record_format | dspace |
| spelling | 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 |
| 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 |
| title | 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_short | 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 |
| url | http://psasir.upm.edu.my/id/eprint/89328/1/NMR.pdf |
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