Computational design of environmental sensors for the potent opioid fentanyl

Bick, Matthew J.; Greisen, Per J.; Morey, Kevin J.; Antunes, Mauricio S.; La, David; Sankaran, Banumathi; Reymond, Luc; Johnsson, Kai; Medford, June I.; Baker, David

doi:10.7554/eLife.28909

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

Journal Article · 18 September 2017 · eLife

DOI: https://doi.org/10.7554/eLife.28909 · OSTI ID:1392706

^[1]; Greisen, Per J. ^[1]; Morey, Kevin J. ^[2]; Antunes, Mauricio S. ^[2]; La, David ^[1]; Sankaran, Banumathi ^[3]; Reymond, Luc ^[4]; Johnsson, Kai ^[4]; Medford, June I. ^[2];

^[5]

Department of Biochemistry, University of Washington, Seattle, United States
Department of Biology, Colorado State University, Fort Collins, United States
Molecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, United States
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
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.

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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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