Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin.
Water is often found to mediate interactions between a ligand and a protein. It can play a significant role in orientating the ligand within a binding pocket and contribute to the free energy of binding. It would thus be extremely useful to be able to accurately predict the position and orientation...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2017
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| _version_ | 1797086476643598336 |
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| author | Sridhar, A Ross, G Biggin, P |
| author_facet | Sridhar, A Ross, G Biggin, P |
| author_sort | Sridhar, A |
| collection | OXFORD |
| description | Water is often found to mediate interactions between a ligand and a protein. It can play a significant role in orientating the ligand within a binding pocket and contribute to the free energy of binding. It would thus be extremely useful to be able to accurately predict the position and orientation of water molecules within a binding pocket. Recently, we developed the WaterDock protocol that was able to predict 97% of the water molecules in a test set. However, this approach generated false positives at a rate of over 20% in most cases and whilst this might be acceptable for some applications, in high throughput scenarios this is not desirable. Here we tackle this problem via the inclusion of knowledge regarding the solvation structure of ligand functional groups. We call this new protocol WaterDock2 and demonstrate that this protocol maintains a similar true positive rate to the original implementation but is capable of reducing the false-positive rate by over 50%. To improve the usability of the method, we have also developed a plugin for the popular graphics program PyMOL. The plugin also contains an implementation of the original WaterDock. |
| first_indexed | 2024-03-07T02:22:35Z |
| format | Journal article |
| id | oxford-uuid:a475d60d-1852-4fd9-bf0e-698557f5f694 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:22:35Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:a475d60d-1852-4fd9-bf0e-698557f5f6942022-03-27T02:33:57ZWaterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a475d60d-1852-4fd9-bf0e-698557f5f694EnglishSymplectic Elements at OxfordPublic Library of Science2017Sridhar, ARoss, GBiggin, PWater is often found to mediate interactions between a ligand and a protein. It can play a significant role in orientating the ligand within a binding pocket and contribute to the free energy of binding. It would thus be extremely useful to be able to accurately predict the position and orientation of water molecules within a binding pocket. Recently, we developed the WaterDock protocol that was able to predict 97% of the water molecules in a test set. However, this approach generated false positives at a rate of over 20% in most cases and whilst this might be acceptable for some applications, in high throughput scenarios this is not desirable. Here we tackle this problem via the inclusion of knowledge regarding the solvation structure of ligand functional groups. We call this new protocol WaterDock2 and demonstrate that this protocol maintains a similar true positive rate to the original implementation but is capable of reducing the false-positive rate by over 50%. To improve the usability of the method, we have also developed a plugin for the popular graphics program PyMOL. The plugin also contains an implementation of the original WaterDock. |
| spellingShingle | Sridhar, A Ross, G Biggin, P Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin. |
| title | Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin. |
| title_full | Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin. |
| title_fullStr | Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin. |
| title_full_unstemmed | Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin. |
| title_short | Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin. |
| title_sort | waterdock 2 0 water placement prediction for holo structures with a pymol plugin |
| work_keys_str_mv | AT sridhara waterdock20waterplacementpredictionforholostructureswithapymolplugin AT rossg waterdock20waterplacementpredictionforholostructureswithapymolplugin AT bigginp waterdock20waterplacementpredictionforholostructureswithapymolplugin |