Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach
Among all serious diseases globally, diabetes (type 1 and type 2) still poses a major challenge to the world population. Several target proteins have been identified, and the etiology causing diabetes has been reasonably well studied. But, there is still a gap in deciding on the choice of a drug, es...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Korea Genome Organization
2014-12-01
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| Series: | Genomics & Informatics |
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| Online Access: | http://genominfo.org/upload/pdf/gni-12-283.pdf |
| _version_ | 1819063299666345984 |
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| author | Manaswini Jagadeb V Badireenath Konkimalla Surya Narayan Rath Rohit Pritam Das |
| author_facet | Manaswini Jagadeb V Badireenath Konkimalla Surya Narayan Rath Rohit Pritam Das |
| author_sort | Manaswini Jagadeb |
| collection | DOAJ |
| description | Among all serious diseases globally, diabetes (type 1 and type 2) still poses a major challenge to the world population. Several target proteins have been identified, and the etiology causing diabetes has been reasonably well studied. But, there is still a gap in deciding on the choice of a drug, especially when the target is mutated. Mutations in the KCNJ11 gene, encoding the kir6.2 channel, are reported to be associated with congenital hyperinsulinism, having a major impact in causing type 1 diabetes, and due to the lack of its 3D structure, an attempt has been made to predict the structure of kir6.2, applying fold recognition methods. The current work is intended to investigate the affinity of four phytochemicals namely, curcumin (Curcuma longa), genistein (Genista tinctoria), piperine (Piper nigrum), and pterostilbene (Vitis vinifera) in a normal as well as in a mutant kir6.2 model by adopting a molecular docking methodology. The phytochemicals were docked in both wild and mutated kir6.2 models in two rounds: blind docking followed by ATP-binding pocket-specific docking. From the binding pockets, the common interacting amino acid residues participating strongly within the binding pocket were identified and compared. From the study, we conclude that these phytochemicals have strong affinity in both the normal and mutant kir6.2 model. This work would be helpful for further study of the phytochemicals above for the treatment of type 1 diabetes by targeting the kir6.2 channel. |
| first_indexed | 2024-12-21T15:12:28Z |
| format | Article |
| id | doaj.art-afa3913c52184c808110a915763762a8 |
| institution | Directory Open Access Journal |
| issn | 1598-866X 2234-0742 |
| language | English |
| last_indexed | 2024-12-21T15:12:28Z |
| publishDate | 2014-12-01 |
| publisher | Korea Genome Organization |
| record_format | Article |
| series | Genomics & Informatics |
| spelling | doaj.art-afa3913c52184c808110a915763762a82022-12-21T18:59:15ZengKorea Genome OrganizationGenomics & Informatics1598-866X2234-07422014-12-0112428328810.5808/GI.2014.12.4.283121Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking ApproachManaswini Jagadeb0V Badireenath Konkimalla1Surya Narayan Rath2Rohit Pritam Das3BIF Centre, Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar 751003, India.School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar 751005, India.BIF Centre, Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar 751003, India.BIF Centre, Department of Bioinformatics, Orissa University of Agriculture and Technology, Bhubaneswar 751003, India.Among all serious diseases globally, diabetes (type 1 and type 2) still poses a major challenge to the world population. Several target proteins have been identified, and the etiology causing diabetes has been reasonably well studied. But, there is still a gap in deciding on the choice of a drug, especially when the target is mutated. Mutations in the KCNJ11 gene, encoding the kir6.2 channel, are reported to be associated with congenital hyperinsulinism, having a major impact in causing type 1 diabetes, and due to the lack of its 3D structure, an attempt has been made to predict the structure of kir6.2, applying fold recognition methods. The current work is intended to investigate the affinity of four phytochemicals namely, curcumin (Curcuma longa), genistein (Genista tinctoria), piperine (Piper nigrum), and pterostilbene (Vitis vinifera) in a normal as well as in a mutant kir6.2 model by adopting a molecular docking methodology. The phytochemicals were docked in both wild and mutated kir6.2 models in two rounds: blind docking followed by ATP-binding pocket-specific docking. From the binding pockets, the common interacting amino acid residues participating strongly within the binding pocket were identified and compared. From the study, we conclude that these phytochemicals have strong affinity in both the normal and mutant kir6.2 model. This work would be helpful for further study of the phytochemicals above for the treatment of type 1 diabetes by targeting the kir6.2 channel.http://genominfo.org/upload/pdf/gni-12-283.pdfdiabetes mellituskir6.2 channelmolecular docking simulationmutationsphytochemicals |
| spellingShingle | Manaswini Jagadeb V Badireenath Konkimalla Surya Narayan Rath Rohit Pritam Das Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach Genomics & Informatics diabetes mellitus kir6.2 channel molecular docking simulation mutations phytochemicals |
| title | Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach |
| title_full | Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach |
| title_fullStr | Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach |
| title_full_unstemmed | Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach |
| title_short | Elucidation of the Inhibitory Effect of Phytochemicals with Kir6.2 Wild-Type and Mutant Models Associated in Type-1 Diabetes through Molecular Docking Approach |
| title_sort | elucidation of the inhibitory effect of phytochemicals with kir6 2 wild type and mutant models associated in type 1 diabetes through molecular docking approach |
| topic | diabetes mellitus kir6.2 channel molecular docking simulation mutations phytochemicals |
| url | http://genominfo.org/upload/pdf/gni-12-283.pdf |
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