Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh
© 2016 American Chemical Society. Structures of several voltage-gated sodium (Na V ) channels from bacteria have been determined recently, but the same feat might not be achieved for the mammalian counterparts in the near future. Thus, at present, computational studies of the mammalian Na V channel...
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| Format: | Journal Article |
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American Chemical Society
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/58297 |
| _version_ | 1848760224324780032 |
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| author | Patel, Dharmeshkumar Mahdavi, S. Kuyucak, S. |
| author_facet | Patel, Dharmeshkumar Mahdavi, S. Kuyucak, S. |
| author_sort | Patel, Dharmeshkumar |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2016 American Chemical Society. Structures of several voltage-gated sodium (Na V ) channels from bacteria have been determined recently, but the same feat might not be achieved for the mammalian counterparts in the near future. Thus, at present, computational studies of the mammalian Na V channels have to be performed using homology models based on the bacterial crystal structures. A successful homology model for the mammalian Na V 1.4 channel was recently constructed using the extensive mutation data for binding of µ-conotoxin GIIIA to Na V 1.4, which was further validated through studies of binding of other µ-conotoxins and ion permeation. Understanding the similarities and differences between the bacterial and mammalian Na V channels is an important issue, and the Na V 1.4-GIIIA system provides a good opportunity for such a comparison. To this end, we study the binding of GIIIA to the bacterial channels Na V Ab and Na V Rh. The complex structures are obtained using docking and molecular dynamics simulations, and the dissociation of GIIIA is studied through umbrella sampling simulations. The results are compared to those obtained from the Na V 1.4-GIIIA system, and the differences in the binding modes arising from the changes in the selectivity filters are highlighted. |
| first_indexed | 2025-11-14T10:12:23Z |
| format | Journal Article |
| id | curtin-20.500.11937-58297 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:12:23Z |
| publishDate | 2016 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-582972023-08-02T06:39:10Z Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh Patel, Dharmeshkumar Mahdavi, S. Kuyucak, S. © 2016 American Chemical Society. Structures of several voltage-gated sodium (Na V ) channels from bacteria have been determined recently, but the same feat might not be achieved for the mammalian counterparts in the near future. Thus, at present, computational studies of the mammalian Na V channels have to be performed using homology models based on the bacterial crystal structures. A successful homology model for the mammalian Na V 1.4 channel was recently constructed using the extensive mutation data for binding of µ-conotoxin GIIIA to Na V 1.4, which was further validated through studies of binding of other µ-conotoxins and ion permeation. Understanding the similarities and differences between the bacterial and mammalian Na V channels is an important issue, and the Na V 1.4-GIIIA system provides a good opportunity for such a comparison. To this end, we study the binding of GIIIA to the bacterial channels Na V Ab and Na V Rh. The complex structures are obtained using docking and molecular dynamics simulations, and the dissociation of GIIIA is studied through umbrella sampling simulations. The results are compared to those obtained from the Na V 1.4-GIIIA system, and the differences in the binding modes arising from the changes in the selectivity filters are highlighted. 2016 Journal Article http://hdl.handle.net/20.500.11937/58297 10.1021/acs.biochem.5b01324 American Chemical Society restricted |
| spellingShingle | Patel, Dharmeshkumar Mahdavi, S. Kuyucak, S. Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh |
| title | Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh |
| title_full | Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh |
| title_fullStr | Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh |
| title_full_unstemmed | Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh |
| title_short | Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh |
| title_sort | computational study of binding of �-conotoxin giiia to bacterial sodium channels navab and navrh |
| url | http://hdl.handle.net/20.500.11937/58297 |