Computational design of environmental sensors for the potent opioid fentanyl
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 19, 2017
- Source ID
- 10.7554/elife.28909
Entities
People
- Banumathi Sankaran
- David Baker
- David La
- June I. Medford
- Kai Johnsson
- Kevin J. Morey
- Luc Reymond
- Matthew J Bick
- Mauricio S. Antunes
- Per J Greisen
Organizations
- Carlsberg Foundation
- Colorado State University
- Defense Threat Reduction Agency
- European Molecular Biology Organization
- Howard Hughes Medical Institute
- Lawrence Berkeley National Laboratory
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institutes of Health
- Swiss Federal Institute of Technology in Lausanne
- United States Department of Energy
- University of Washington