Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitors
Abstract Lung cancer is the leading cause of cancer-related fatalities globally, accounting for the highest mortality rate among both men and women. Mutations in the epidermal growth factor receptor (EGFR) gene are frequently found in non-small cell lung cancer (NSCLC). Since curcumin and CB[2]UN su...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-83868-5 |
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| author | Anakha D. Rajeeve Ramasamy Yamuna P. K. Krishnan Namboori |
| author_facet | Anakha D. Rajeeve Ramasamy Yamuna P. K. Krishnan Namboori |
| author_sort | Anakha D. Rajeeve |
| collection | DOAJ |
| description | Abstract Lung cancer is the leading cause of cancer-related fatalities globally, accounting for the highest mortality rate among both men and women. Mutations in the epidermal growth factor receptor (EGFR) gene are frequently found in non-small cell lung cancer (NSCLC). Since curcumin and CB[2]UN support various medicinal applications in drug delivery and design, we investigated the effect of curcumin and CB[2]UN-based drugs in controlling EGFR-mutant NSCLC through a dodecagonal computational approach. Molecular docking studies revealed that the ligands curcumin (-6.9 kcal/mol) and CB[2]UN (-8.1 kcal/mol) bound more strongly to the EGFR-mutant NSCLC proteins with 2ITX and 2ITV, respectively. Molecular dynamics simulation (50 ns) investigation of protein-ligand complexes using RMSD, RMSF, Rg, and SASA indicated that curcumin and CB[2]UN with EGFR-mutant proteins are kinetically stable. In addition, MMPBSA/MMGBSA analysis confirmed the thermodynamic stability of each curcumin and CB[2]UN protein-ligand complex. Finally, KDeep absolute binding affinity calculations show energies of -6.13 kcal/mol and − 5.26 kcal/mol for 2ITX-CUR and 2ITV-CB[2]UN protein-ligand complexes, respectively. Thus, our dodecagonal strategy reveals that 2ITX-CUR and 2ITV-CB[2]UN are more likely to form protein-ligand complexes with more significant binding affinities and excellent stability throughout the 50 ns simulation time. |
| format | Article |
| id | doaj-art-49e5dae9a3ac446192525f12eb9f910e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-49e5dae9a3ac446192525f12eb9f910e2025-02-02T12:17:06ZengNature PortfolioScientific Reports2045-23222025-01-0115112210.1038/s41598-024-83868-5Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitorsAnakha D. Rajeeve0Ramasamy Yamuna1P. K. Krishnan Namboori2Department of Chemistry, Amrita School of Physical Sciences Coimbatore, Amrita Vishwa VidyapeethamDepartment of Chemistry, Amrita School of Physical Sciences Coimbatore, Amrita Vishwa VidyapeethamAmrita School of Artificial Intelligences, Coimbatore, Amrita Vishwa VidyapeethamAbstract Lung cancer is the leading cause of cancer-related fatalities globally, accounting for the highest mortality rate among both men and women. Mutations in the epidermal growth factor receptor (EGFR) gene are frequently found in non-small cell lung cancer (NSCLC). Since curcumin and CB[2]UN support various medicinal applications in drug delivery and design, we investigated the effect of curcumin and CB[2]UN-based drugs in controlling EGFR-mutant NSCLC through a dodecagonal computational approach. Molecular docking studies revealed that the ligands curcumin (-6.9 kcal/mol) and CB[2]UN (-8.1 kcal/mol) bound more strongly to the EGFR-mutant NSCLC proteins with 2ITX and 2ITV, respectively. Molecular dynamics simulation (50 ns) investigation of protein-ligand complexes using RMSD, RMSF, Rg, and SASA indicated that curcumin and CB[2]UN with EGFR-mutant proteins are kinetically stable. In addition, MMPBSA/MMGBSA analysis confirmed the thermodynamic stability of each curcumin and CB[2]UN protein-ligand complex. Finally, KDeep absolute binding affinity calculations show energies of -6.13 kcal/mol and − 5.26 kcal/mol for 2ITX-CUR and 2ITV-CB[2]UN protein-ligand complexes, respectively. Thus, our dodecagonal strategy reveals that 2ITX-CUR and 2ITV-CB[2]UN are more likely to form protein-ligand complexes with more significant binding affinities and excellent stability throughout the 50 ns simulation time.https://doi.org/10.1038/s41598-024-83868-5Lung cancerEGFRCucurbiturilDodecagonal strategyMultitargeted inhibitorsMolecular dynamics simulation |
| spellingShingle | Anakha D. Rajeeve Ramasamy Yamuna P. K. Krishnan Namboori Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitors Scientific Reports Lung cancer EGFR Cucurbituril Dodecagonal strategy Multitargeted inhibitors Molecular dynamics simulation |
| title | Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitors |
| title_full | Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitors |
| title_fullStr | Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitors |
| title_full_unstemmed | Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitors |
| title_short | Elucidating the potential of EGFR mutated NSCLC and identifying its multitargeted inhibitors |
| title_sort | elucidating the potential of egfr mutated nsclc and identifying its multitargeted inhibitors |
| topic | Lung cancer EGFR Cucurbituril Dodecagonal strategy Multitargeted inhibitors Molecular dynamics simulation |
| url | https://doi.org/10.1038/s41598-024-83868-5 |
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