Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process
<div><p>The BRAF gene is responsible for transferring signals from outside of the cell to inside of the nucleus by converting a protein namely B-Raf through the RAS/MAPK pathway. This pathway contribute to cell division, proliferation, migration, and apoptotic cell death of human and ani...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2022
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| الموضوعات: | |
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| _version_ | 1864513519062351872 |
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| author | F. A. Dain Md Opo (18418845) |
| author2 | Ahad Amer Alsaiari (13902165) Mohammad Habibur Rahman Molla (18418848) Md Afsar Ahmed Sumon (18418851) Khaled A. Yaghmour (13902174) Foysal Ahammad (9286524) Farhan Mohammad (256409) Jesus Simal-Gandara (10918888) |
| author2_role | author author author author author author author |
| author_facet | F. A. Dain Md Opo (18418845) Ahad Amer Alsaiari (13902165) Mohammad Habibur Rahman Molla (18418848) Md Afsar Ahmed Sumon (18418851) Khaled A. Yaghmour (13902174) Foysal Ahammad (9286524) Farhan Mohammad (256409) Jesus Simal-Gandara (10918888) |
| author_role | author |
| dc.creator.none.fl_str_mv | F. A. Dain Md Opo (18418845) Ahad Amer Alsaiari (13902165) Mohammad Habibur Rahman Molla (18418848) Md Afsar Ahmed Sumon (18418851) Khaled A. Yaghmour (13902174) Foysal Ahammad (9286524) Farhan Mohammad (256409) Jesus Simal-Gandara (10918888) |
| dc.date.none.fl_str_mv | 2022-10-04T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fchem.2022.986376 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Identification_of_novel_natural_drug_candidates_against_BRAF_mutated_carcinoma_An_integrative_in-silico_structure-based_pharmacophore_modeling_and_virtual_screening_process/25659105 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Chemical sciences Analytical chemistry pharmacophore modeling virtual screening molecular docking molecular dynamics simulation BRAF B-Raf |
| dc.title.none.fl_str_mv | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>The BRAF gene is responsible for transferring signals from outside of the cell to inside of the nucleus by converting a protein namely B-Raf through the RAS/MAPK pathway. This pathway contribute to cell division, proliferation, migration, and apoptotic cell death of human and animal. Mutation in this gene may cause the development of several cancers, including lung, skin, colon, and neuroblastoma. Currently, a few available drugs are being used that has developed by targeting the BRAF mutated protein, and due to the toxic side effects, patients suffer a lot during their treatment. Therefore this study aimed to identify potentially lead compounds that can target and block the expression of BRAF and subsequently inhibit the cancer. The hits were generated through the pharmacophore model-based virtual screening, molecular docking, pharmacohore model validation, ADME (absorption, distribution, metabolism, and excretion) analysis molecular dynamics (MD) simulation to find more suitable candidate against the overexpress BRAF gene. The pharmacophore based screening initially identified 14 k possible hits from online database which were further screened by ligand scout advance software to get hit compound. Based on molecular docking score of ZINC70454679 (-10.6 kcal/mol), ZINC253500968 (-9.4 kcal/mol), ZINC106887736 (-8.6 kcal/mol), and ZINC107434492 (-8.1 kcal/mol), pharmacophore feature and toxicity evaluation, we selected four possible lead compounds. The dynamic simulation with Schrodinger Maestro software was used to determine the stability of the potential lead candidates with target protein (PDB ID: 5VAM). The results showed that the newly obtained four compounds were more stable than the control ligand (Pub Chem ID: 90408826). The current results showed that the ZINC70454679, ZINC253500968, ZINC106887736, and ZINC107434492 compounds may be able to work against several cancers through targeting the BRAF overexpressed gene. To develop a novel drug candidate, however the evaluation of the web lab based experimental work are necessary to evaluate the efficiency of the each compound against the BRAF target gene.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Chemistry<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fchem.2022.986376" target="_blank">https://dx.doi.org/10.3389/fchem.2022.986376</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_915f3a49cd39bc067363ed13936561f3 |
| identifier_str_mv | 10.3389/fchem.2022.986376 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25659105 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening processF. A. Dain Md Opo (18418845)Ahad Amer Alsaiari (13902165)Mohammad Habibur Rahman Molla (18418848)Md Afsar Ahmed Sumon (18418851)Khaled A. Yaghmour (13902174)Foysal Ahammad (9286524)Farhan Mohammad (256409)Jesus Simal-Gandara (10918888)Chemical sciencesAnalytical chemistrypharmacophore modelingvirtual screeningmolecular dockingmolecular dynamics simulationBRAFB-Raf<div><p>The BRAF gene is responsible for transferring signals from outside of the cell to inside of the nucleus by converting a protein namely B-Raf through the RAS/MAPK pathway. This pathway contribute to cell division, proliferation, migration, and apoptotic cell death of human and animal. Mutation in this gene may cause the development of several cancers, including lung, skin, colon, and neuroblastoma. Currently, a few available drugs are being used that has developed by targeting the BRAF mutated protein, and due to the toxic side effects, patients suffer a lot during their treatment. Therefore this study aimed to identify potentially lead compounds that can target and block the expression of BRAF and subsequently inhibit the cancer. The hits were generated through the pharmacophore model-based virtual screening, molecular docking, pharmacohore model validation, ADME (absorption, distribution, metabolism, and excretion) analysis molecular dynamics (MD) simulation to find more suitable candidate against the overexpress BRAF gene. The pharmacophore based screening initially identified 14 k possible hits from online database which were further screened by ligand scout advance software to get hit compound. Based on molecular docking score of ZINC70454679 (-10.6 kcal/mol), ZINC253500968 (-9.4 kcal/mol), ZINC106887736 (-8.6 kcal/mol), and ZINC107434492 (-8.1 kcal/mol), pharmacophore feature and toxicity evaluation, we selected four possible lead compounds. The dynamic simulation with Schrodinger Maestro software was used to determine the stability of the potential lead candidates with target protein (PDB ID: 5VAM). The results showed that the newly obtained four compounds were more stable than the control ligand (Pub Chem ID: 90408826). The current results showed that the ZINC70454679, ZINC253500968, ZINC106887736, and ZINC107434492 compounds may be able to work against several cancers through targeting the BRAF overexpressed gene. To develop a novel drug candidate, however the evaluation of the web lab based experimental work are necessary to evaluate the efficiency of the each compound against the BRAF target gene.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Chemistry<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fchem.2022.986376" target="_blank">https://dx.doi.org/10.3389/fchem.2022.986376</a></p>2022-10-04T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fchem.2022.986376https://figshare.com/articles/journal_contribution/Identification_of_novel_natural_drug_candidates_against_BRAF_mutated_carcinoma_An_integrative_in-silico_structure-based_pharmacophore_modeling_and_virtual_screening_process/25659105CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256591052022-10-04T03:00:00Z |
| spellingShingle | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process F. A. Dain Md Opo (18418845) Chemical sciences Analytical chemistry pharmacophore modeling virtual screening molecular docking molecular dynamics simulation BRAF B-Raf |
| status_str | publishedVersion |
| title | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process |
| title_full | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process |
| title_fullStr | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process |
| title_full_unstemmed | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process |
| title_short | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process |
| title_sort | Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process |
| topic | Chemical sciences Analytical chemistry pharmacophore modeling virtual screening molecular docking molecular dynamics simulation BRAF B-Raf |