Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies
Numerous malignancies, including breast cancer, non-small cell lung cancer, and chronic myeloid leukemia, are brought on by aberrant tyrosine kinase signaling. Since the current chemotherapeutic medicines are toxic, there is a great need and demand from cancer patients to find novel chemicals that a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English English |
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Taylor & Francis
2023
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| Online Access: | http://umpir.ump.edu.my/id/eprint/41756/ http://umpir.ump.edu.my/id/eprint/41756/1/Computer-aided%20anti-cancer%20drug%20discovery%20of%20EGFR%20protein%20based%20on%20virtual%20screening%20of%20drug%20bank%2C%20ADMET%2C%20docking%2C%20DFT.pdf http://umpir.ump.edu.my/id/eprint/41756/2/Computer-aided%20anti-cancer%20drug%20discovery%20of%20EGFR%20protein%20based%20on%20virtual%20screening%20of%20drug%20bank%2C%20ADMET%2C%20docking%2C%20DFT%20and%20molecular%20dynamic%20simulation%20studies.pdf |
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| author | Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Saiful Nizam, Tajuddin Mohd Fadhlizil Fasihi, Mohd Aluwi Huq, A. K. M. Moyeenul |
| author_facet | Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Saiful Nizam, Tajuddin Mohd Fadhlizil Fasihi, Mohd Aluwi Huq, A. K. M. Moyeenul |
| author_sort | Roney, Miah |
| building | UMP Institutional Repository |
| collection | Online Access |
| description | Numerous malignancies, including breast cancer, non-small cell lung cancer, and chronic myeloid leukemia, are brought on by aberrant tyrosine kinase signaling. Since the current chemotherapeutic medicines are toxic, there is a great need and demand from cancer patients to find novel chemicals that are toxic-free or have low toxicity and that can kill tumor cells and stop their growth. This work describes the in-silico examination of substances from the drug bank as EGFR inhibitors. Firstly, drug-bank was screened using the pharmacophore technique to select the ligands and Erlotinib (DB00530) was used as matrix compound. The selected ligands were screened using ADMET and the hit compounds were subjected to docking. The lead compound from the docking was subjected to DFT and MD simulation study. Using the pharmacophore technique, 23 compounds were found through virtual drug bank screening. One hit molecule from the ADMET prediction was the subject of docking study. According to the findings, DB03365 molecule fits to the EGFR active site by several hydrogen bonding interactions with amino acids. Furthermore, DFT analysis revealed high reactivity for DB03365 compound in the binding pocket of the target protein, based on ELUMO, EHOMO and band energy gap. Furthermore, MD simulations for 100 ns revealed that the ligand interactions with the residues of EGFR protein were part of the essential residues for structural stability and functionality. However, DB03365 was a promising lead molecule that outperformed the reference compound in terms of performance and in-vitro and in-vivo experiments needs to validate the study. |
| first_indexed | 2025-11-15T03:44:35Z |
| format | Article |
| id | ump-41756 |
| institution | Universiti Malaysia Pahang |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-15T03:44:35Z |
| publishDate | 2023 |
| publisher | Taylor & Francis |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | ump-417562024-07-01T06:41:06Z http://umpir.ump.edu.my/id/eprint/41756/ Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Saiful Nizam, Tajuddin Mohd Fadhlizil Fasihi, Mohd Aluwi Huq, A. K. M. Moyeenul HD Industries. Land use. Labor R Medicine (General) Numerous malignancies, including breast cancer, non-small cell lung cancer, and chronic myeloid leukemia, are brought on by aberrant tyrosine kinase signaling. Since the current chemotherapeutic medicines are toxic, there is a great need and demand from cancer patients to find novel chemicals that are toxic-free or have low toxicity and that can kill tumor cells and stop their growth. This work describes the in-silico examination of substances from the drug bank as EGFR inhibitors. Firstly, drug-bank was screened using the pharmacophore technique to select the ligands and Erlotinib (DB00530) was used as matrix compound. The selected ligands were screened using ADMET and the hit compounds were subjected to docking. The lead compound from the docking was subjected to DFT and MD simulation study. Using the pharmacophore technique, 23 compounds were found through virtual drug bank screening. One hit molecule from the ADMET prediction was the subject of docking study. According to the findings, DB03365 molecule fits to the EGFR active site by several hydrogen bonding interactions with amino acids. Furthermore, DFT analysis revealed high reactivity for DB03365 compound in the binding pocket of the target protein, based on ELUMO, EHOMO and band energy gap. Furthermore, MD simulations for 100 ns revealed that the ligand interactions with the residues of EGFR protein were part of the essential residues for structural stability and functionality. However, DB03365 was a promising lead molecule that outperformed the reference compound in terms of performance and in-vitro and in-vivo experiments needs to validate the study. Taylor & Francis 2023 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/41756/1/Computer-aided%20anti-cancer%20drug%20discovery%20of%20EGFR%20protein%20based%20on%20virtual%20screening%20of%20drug%20bank%2C%20ADMET%2C%20docking%2C%20DFT.pdf pdf en http://umpir.ump.edu.my/id/eprint/41756/2/Computer-aided%20anti-cancer%20drug%20discovery%20of%20EGFR%20protein%20based%20on%20virtual%20screening%20of%20drug%20bank%2C%20ADMET%2C%20docking%2C%20DFT%20and%20molecular%20dynamic%20simulation%20studies.pdf Roney, Miah and Dubey, Amit and Muhammad Hassan, Nasir and Tufail, Aisha and Saiful Nizam, Tajuddin and Mohd Fadhlizil Fasihi, Mohd Aluwi and Huq, A. K. M. Moyeenul (2023) Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies. Journal of Biomolecular Structure and Dynamics. pp. 1-16. ISSN 0739-1102. (In Press / Online First) (In Press / Online First) https://doi.org/10.1080/07391102.2023.2252092 10.1080/07391102.2023.2252092 |
| spellingShingle | HD Industries. Land use. Labor R Medicine (General) Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Saiful Nizam, Tajuddin Mohd Fadhlizil Fasihi, Mohd Aluwi Huq, A. K. M. Moyeenul Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies |
| title | Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies |
| title_full | Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies |
| title_fullStr | Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies |
| title_full_unstemmed | Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies |
| title_short | Computer-aided anti-cancer drug discovery of EGFR protein based on virtual screening of drug bank, ADMET, docking, DFT and molecular dynamic simulation studies |
| title_sort | computer-aided anti-cancer drug discovery of egfr protein based on virtual screening of drug bank, admet, docking, dft and molecular dynamic simulation studies |
| topic | HD Industries. Land use. Labor R Medicine (General) |
| url | http://umpir.ump.edu.my/id/eprint/41756/ http://umpir.ump.edu.my/id/eprint/41756/ http://umpir.ump.edu.my/id/eprint/41756/ http://umpir.ump.edu.my/id/eprint/41756/1/Computer-aided%20anti-cancer%20drug%20discovery%20of%20EGFR%20protein%20based%20on%20virtual%20screening%20of%20drug%20bank%2C%20ADMET%2C%20docking%2C%20DFT.pdf http://umpir.ump.edu.my/id/eprint/41756/2/Computer-aided%20anti-cancer%20drug%20discovery%20of%20EGFR%20protein%20based%20on%20virtual%20screening%20of%20drug%20bank%2C%20ADMET%2C%20docking%2C%20DFT%20and%20molecular%20dynamic%20simulation%20studies.pdf |