Computational design of environmental sensors for the potent opioid fentanyl
We describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structure...
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eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/28909 |
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doaj-318860fd73d04bffacfc4c21510e0e192021-05-05T13:48:56ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.28909Computational design of environmental sensors for the potent opioid fentanylMatthew J Bick0https://orcid.org/0000-0002-9585-859XPer J Greisen1Kevin J Morey2Mauricio S Antunes3David La4Banumathi Sankaran5Luc Reymond6Kai Johnsson7June I Medford8David Baker9https://orcid.org/0000-0001-7896-6217Department of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biology, Colorado State University, Fort Collins, United StatesDepartment of Biology, Colorado State University, Fort Collins, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesMolecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, United StatesEcole Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, Lausanne, Switzerland; Department of Chemical Biology, Max-Planck-Institute for Medical Research, Heidelberg, GermanyEcole Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, Lausanne, Switzerland; Department of Chemical Biology, Max-Planck-Institute for Medical Research, Heidelberg, GermanyDepartment of Biology, Colorado State University, Fort Collins, United StatesDepartment of Biochemistry, University of Washington, Seattle, United States; Howard Hughes Medical Institute, University of Washington, Seattle, United StatesWe describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structures of the highest affinity binder reveal a highly preorganized binding site, and an overall architecture and ligand placement in close agreement with the design model. We use the designs to generate plant sensors for fentanyl by coupling ligand binding to design stability. The method should be generally useful for detecting toxic hydrophobic compounds in the environment.https://elifesciences.org/articles/28909protein designbiosensorstransgenic plants |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Matthew J Bick Per J Greisen Kevin J Morey Mauricio S Antunes David La Banumathi Sankaran Luc Reymond Kai Johnsson June I Medford David Baker |
| spellingShingle |
Matthew J Bick Per J Greisen Kevin J Morey Mauricio S Antunes David La Banumathi Sankaran Luc Reymond Kai Johnsson June I Medford David Baker Computational design of environmental sensors for the potent opioid fentanyl eLife protein design biosensors transgenic plants |
| author_facet |
Matthew J Bick Per J Greisen Kevin J Morey Mauricio S Antunes David La Banumathi Sankaran Luc Reymond Kai Johnsson June I Medford David Baker |
| author_sort |
Matthew J Bick |
| title |
Computational design of environmental sensors for the potent opioid fentanyl |
| title_short |
Computational design of environmental sensors for the potent opioid fentanyl |
| title_full |
Computational design of environmental sensors for the potent opioid fentanyl |
| title_fullStr |
Computational design of environmental sensors for the potent opioid fentanyl |
| title_full_unstemmed |
Computational design of environmental sensors for the potent opioid fentanyl |
| title_sort |
computational design of environmental sensors for the potent opioid fentanyl |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2017-09-01 |
| description |
We describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structures of the highest affinity binder reveal a highly preorganized binding site, and an overall architecture and ligand placement in close agreement with the design model. We use the designs to generate plant sensors for fentanyl by coupling ligand binding to design stability. The method should be generally useful for detecting toxic hydrophobic compounds in the environment. |
| topic |
protein design biosensors transgenic plants |
| url |
https://elifesciences.org/articles/28909 |
| work_keys_str_mv |
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