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 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.
| Errataetall: |
ErratumIn: Future Med Chem. 2020 Oct;12(20):1885. - PMID 33032463 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Future medicinal chemistry - 12(2020), 18 vom: 06. Sept., Seite 1611-1631 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Quah, Shun Ying [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.07.2021 Date Revised 14.07.2021 published: Print-Electronic ErratumIn: Future Med Chem. 2020 Oct;12(20):1885. - PMID 33032463 Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2020-0104 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314653805 |
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| 500 | |a ErratumIn: Future Med Chem. 2020 Oct;12(20):1885. - PMID 33032463 | ||
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| 520 | |a 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 | ||
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| 700 | 1 | |a Deb, Pran Kishore |e verfasserin |4 aut | |
| 700 | 1 | |a Sagineedu, Sreenivasa Rao |e verfasserin |4 aut | |
| 700 | 1 | |a Stanslas, Johnson |e verfasserin |4 aut | |
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