Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption
Structural basis for exploration into MDM2 and MDM2-DHFR interaction plays a vital role in analyzing the obstruction in folate metabolism, nonsynthesis of purines, and further epigenetic regulation in Homo sapiens. Therefore, it leads to suppression of normal cellular behavior and malignancy. This h...
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Wiley
2016-01-01
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| Series: | Scientifica |
| Online Access: | http://dx.doi.org/10.1155/2016/9420692 |
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| author | Arundhati Banerjee Sujay Ray |
| author_facet | Arundhati Banerjee Sujay Ray |
| author_sort | Arundhati Banerjee |
| collection | DOAJ |
| description | Structural basis for exploration into MDM2 and MDM2-DHFR interaction plays a vital role in analyzing the obstruction in folate metabolism, nonsynthesis of purines, and further epigenetic regulation in Homo sapiens. Therefore, it leads to suppression of normal cellular behavior and malignancy. This has been earlier documented via yeast two-hybrid assays. So, with a novel outlook, this study explores the molecular level demonstration of the best satisfactory MDM2 model selection after performing manifold modeling techniques. Z-scores and other stereochemical features were estimated for comparison. Further, protein-protein docking was executed with MDM2 and the experimentally validated X-ray crystallographic DHFR. Residual disclosure from the best suited simulated protein complex disclosed 18 side chain and 3 ionic interactions to strongly accommodate MDM2 protein into the pocket-like zone in DHFR due to the positive environment by charged residues. Lysine residues from MDM2 played a predominant role. Moreover, evaluation from varied energy calculations, folding rate, and net area for solvent accessibility implied the active participation of MDM2 with DHFR. Fascinatingly, conformational transitions from coils to helices and β-sheets after interaction with DHFR affirm the conformational strength and firmer interaction of human MDM2-DHFR. Therefore, this probe instigates near-future clinical research and interactive computational investigations with mutations. |
| format | Article |
| id | doaj-art-a822b201bf4349b6a92da149a6a02e60 |
| institution | Kabale University |
| issn | 2090-908X |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
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| spelling | doaj-art-a822b201bf4349b6a92da149a6a02e602025-02-03T00:59:24ZengWileyScientifica2090-908X2016-01-01201610.1155/2016/94206929420692Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic DisruptionArundhati Banerjee0Sujay Ray1Department of Biotechnology, National Institute of Technology, Mahatma Gandhi Avenue, Durgapur, West Bengal 713209, IndiaDepartment of Biochemistry and Biophysics, University of Kalyani, Kalyani, Nadia, West Bengal 741235, IndiaStructural basis for exploration into MDM2 and MDM2-DHFR interaction plays a vital role in analyzing the obstruction in folate metabolism, nonsynthesis of purines, and further epigenetic regulation in Homo sapiens. Therefore, it leads to suppression of normal cellular behavior and malignancy. This has been earlier documented via yeast two-hybrid assays. So, with a novel outlook, this study explores the molecular level demonstration of the best satisfactory MDM2 model selection after performing manifold modeling techniques. Z-scores and other stereochemical features were estimated for comparison. Further, protein-protein docking was executed with MDM2 and the experimentally validated X-ray crystallographic DHFR. Residual disclosure from the best suited simulated protein complex disclosed 18 side chain and 3 ionic interactions to strongly accommodate MDM2 protein into the pocket-like zone in DHFR due to the positive environment by charged residues. Lysine residues from MDM2 played a predominant role. Moreover, evaluation from varied energy calculations, folding rate, and net area for solvent accessibility implied the active participation of MDM2 with DHFR. Fascinatingly, conformational transitions from coils to helices and β-sheets after interaction with DHFR affirm the conformational strength and firmer interaction of human MDM2-DHFR. Therefore, this probe instigates near-future clinical research and interactive computational investigations with mutations.http://dx.doi.org/10.1155/2016/9420692 |
| spellingShingle | Arundhati Banerjee Sujay Ray Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption Scientifica |
| title | Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption |
| title_full | Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption |
| title_fullStr | Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption |
| title_full_unstemmed | Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption |
| title_short | Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption |
| title_sort | structural exploration and conformational transitions in mdm2 upon dhfr interaction from homo sapiens a computational outlook for malignancy via epigenetic disruption |
| url | http://dx.doi.org/10.1155/2016/9420692 |
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