Format

Send to

Choose Destination
Elife. 2017 Sep 19;6. pii: e28909. doi: 10.7554/eLife.28909.

Computational design of environmental sensors for the potent opioid fentanyl.

Author information

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.
5
Department of Chemical Biology, Max-Planck-Institute for Medical Research, Heidelberg, Germany.
6
Howard Hughes Medical Institute, University of Washington, Seattle, United States.
#
Contributed equally

Abstract

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.

KEYWORDS:

A. thaliana; E. coli; S. cerevisiae; biochemistry; biosensors; computational biology; protein design; systems biology; transgenic plants

PMID:
28925919
PMCID:
PMC5655540
DOI:
10.7554/eLife.28909
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center