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Title: Computational design of environmental sensors for the potent opioid fentanyl

Journal Article · · eLife
ORCiD logo [1];  [1];  [2];  [2];  [1];  [3];  [4];  [4];  [2]; ORCiD logo [5]
  1. Department of Biochemistry, University of Washington, Seattle, United States
  2. Department of Biology, Colorado State University, Fort Collins, United States
  3. Molecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, United States
  4. Ecole Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, Lausanne, Switzerland, Department of Chemical Biology, Max-Planck-Institute for Medical Research, Heidelberg, Germany
  5. Department of Biochemistry, University of Washington, Seattle, United States, Howard Hughes Medical Institute, University of Washington, Seattle, United States

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.

Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1392706
Alternate ID(s):
OSTI ID: 1416923; OSTI ID: 1392707
Journal Information:
eLife, Journal Name: eLife Vol. 6; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English

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