Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanism
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) plays a crucial role in signaling pathways and has emerged as an attractive target for anticancer therapy. Developing small-molecule inhibitors targeting PIK3CA has emerged as a promising therapeutic strategy. Here, we e...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022424000021 |
| _version_ | 1797365615672950784 |
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| author | Taj Mohammad Afzal Hussain Mohamed F. Alajmi Saba Hasan Dharmendra Kumar Yadav Md. Imtaiyaz Hassan |
| author_facet | Taj Mohammad Afzal Hussain Mohamed F. Alajmi Saba Hasan Dharmendra Kumar Yadav Md. Imtaiyaz Hassan |
| author_sort | Taj Mohammad |
| collection | DOAJ |
| description | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) plays a crucial role in signaling pathways and has emerged as an attractive target for anticancer therapy. Developing small-molecule inhibitors targeting PIK3CA has emerged as a promising therapeutic strategy. Here, we employed in-silico approaches to identify potential inhibitors of PIK3CA from a pool of bioactive phytoconstituents available from IMPPAT 2.0 database. The initial screening was based on their drug-like properties and docking score, followed by interaction analysis and 100 nanoseconds (ns) molecular dynamics (MD) simulations to evaluate their conformational stability with PIK3CA. MD simulation studies suggested the formation of stable complexes between PIK3CA and the elucidated compounds Apollinine and Isoglycyrol. These compounds exhibited exceptional drug-like properties, potential binding efficiency, and remarkable stability. The findings suggest that Apollinine and Isoglycyrol could serve as potential leads in the therapeutic development of PIK3CA inhibitors for targeting cancer. Moreover, the insights gained from the simulation dynamics shed light on the molecular mechanisms of PIK3CA inhibition that facilitate the rational design of future inhibitors. |
| first_indexed | 2024-03-08T16:51:29Z |
| format | Article |
| id | doaj.art-e18c49aa2fc54f2c98592dd22040debe |
| institution | Directory Open Access Journal |
| issn | 2667-0224 |
| language | English |
| last_indexed | 2024-03-08T16:51:29Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj.art-e18c49aa2fc54f2c98592dd22040debe2024-01-05T04:25:21ZengElsevierChemical Physics Impact2667-02242024-06-018100458Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanismTaj Mohammad0Afzal Hussain1Mohamed F. Alajmi2Saba Hasan3Dharmendra Kumar Yadav4Md. Imtaiyaz Hassan5Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, IndiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaAmity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, IndiaGachon Institute of Pharmaceutical Science and Department of Pharmacy, College of Pharmacy, Gachon University, Incheon, Republic of Korea; Corresponding authors.Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India; Corresponding authors.Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) plays a crucial role in signaling pathways and has emerged as an attractive target for anticancer therapy. Developing small-molecule inhibitors targeting PIK3CA has emerged as a promising therapeutic strategy. Here, we employed in-silico approaches to identify potential inhibitors of PIK3CA from a pool of bioactive phytoconstituents available from IMPPAT 2.0 database. The initial screening was based on their drug-like properties and docking score, followed by interaction analysis and 100 nanoseconds (ns) molecular dynamics (MD) simulations to evaluate their conformational stability with PIK3CA. MD simulation studies suggested the formation of stable complexes between PIK3CA and the elucidated compounds Apollinine and Isoglycyrol. These compounds exhibited exceptional drug-like properties, potential binding efficiency, and remarkable stability. The findings suggest that Apollinine and Isoglycyrol could serve as potential leads in the therapeutic development of PIK3CA inhibitors for targeting cancer. Moreover, the insights gained from the simulation dynamics shed light on the molecular mechanisms of PIK3CA inhibition that facilitate the rational design of future inhibitors.http://www.sciencedirect.com/science/article/pii/S2667022424000021Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alphaPhytoconstituentsApollinineIsoglycyrolVirtual screening |
| spellingShingle | Taj Mohammad Afzal Hussain Mohamed F. Alajmi Saba Hasan Dharmendra Kumar Yadav Md. Imtaiyaz Hassan Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanism Chemical Physics Impact Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha Phytoconstituents Apollinine Isoglycyrol Virtual screening |
| title | Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanism |
| title_full | Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanism |
| title_fullStr | Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanism |
| title_full_unstemmed | Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanism |
| title_short | Identifying potential inhibitors of phosphatidylinositol 4,5-bisphosphate 3-kinase: Molecular dynamic insights into the interaction and inhibitory mechanism |
| title_sort | identifying potential inhibitors of phosphatidylinositol 4 5 bisphosphate 3 kinase molecular dynamic insights into the interaction and inhibitory mechanism |
| topic | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha Phytoconstituents Apollinine Isoglycyrol Virtual screening |
| url | http://www.sciencedirect.com/science/article/pii/S2667022424000021 |
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