U.S. Department of Energy Office of Biological and Environmental Research

BER Research Highlights


More Designer Peptides, More Possibilities
Published: January 26, 2018
Posted: February 01, 2018

Scientists are more rapidly designing peptides for industrial and medical applications through a complex computational model and real-time testing with the award-winning SLIM ion analysis technology. [Image source: PNNL.]

Combined experimental and modeling approach contributes to understanding the structure of cell membranes and their permeability and provides a basis for biodesign of cellular pathways for therapeutics and other applications.

The Science
With their tiny scaffolds of atoms, peptides hold the promise of creating catalysts for biofuels, capturing hazardous waste, and delivering new therapies to improve health. While nature offers a few peptides with the perfect characteristics to be used for such purposes, scientists have been attempting to design peptides more precisely, expanding biodiversity. The process has been one of slow trial-and-error—build a peptide, test a peptide, start over. Now a team of scientists has blended complex calculations with an award-winning ion analysis technology to rapidly design and test peptides.

The Impact
The approach expanded the number of peptides of potential from only a handful to more than 200, vastly increasing the variety of biological materials custom-designed for industrial and medical applications. The approach also provided a platform through which scientists can test additional peptides and other molecules much more rapidly than previously.

Summary
Scientists from the University of Washington, Stanford University, and the Pacific Northwest National Laboratory (PNNL) created a computational model that allowed them to simulate various types of peptides and identify which were stable enough to be used as scaffolding for industrial and medical purposes. To evaluate their calculations experimentally, they then created the most promising peptides and analyzed them using SLIM (structures for lossless ion manipulations) at the Environmental Molecular Sciences Laboratory (EMSL), a U.S. Department of Energy Office of Science User Facility. Developed by a team of EMSL and other PNNL scientists and winner of the prestigious R&D 100 award for 2017 for the most impactful technologies of the year, SLIM is a versatile, high-throughput, and ultrahigh sensitivity and resolution ion analysis technology that can identify similar molecules with different structures in a small amount of sample. Using SLIM, the team was able to determine which designed peptides were stable enough for industrial and medical applications and how changes in amino acids, the building blocks of peptides, affected the potential use of the peptide. The approach allowed the scientists to accomplish the work in hours instead of days. The resulting comprehensive library of designed peptides will serve as a foundation for future efforts.

Contacts (BER PM)
Paul Bayer, SC-23.1, 301-903-5324

(PI Contact)
David Baker
University of Washington
dabaker@uw.edu
Yehia Ibrahim
Pacific Northwest National Laboratory
Yehia.Ibrahim@pnnl.gov

Funding
This work was supported by the U.S. Department of Energy’s Office of Science, Office of Biological and Environmental Research, including support of the Environmental Molecular Sciences Laboratory (EMSL), a DOE Office of Science User Facility; National Institutes of Health; and the Pacific Northwest National Laboratory’s Laboratory-Directed Research and Development Program.

Publications
Hosseinzadeh, P., G. Bhardwaj, V.K. Mulligan, M.D. Shortridge, T.W. Craven, F. Pardo-Avila, S.A. Rettie, D.E. Kim, D-A. Silva, Y.M. Ibrahim, I.K. Webb, J.R. Cort, J.N. Adkins, G. Varani, and D. Baker. “Comprehensive computational design of ordered peptide macrocycles.” Science 358, 1461-1466(2017). [DOI:10.1126/science.aap7577]

Topic Areas:

  • Research Area: DOE Environmental Molecular Sciences Laboratory (EMSL)
  • Research Area: Biosystems Design
  • Research Area: Computational Biology, Bioinformatics, Modeling
  • Cross-Cutting: Lectures, Awards, and Recognition

Division: SC-23.1 Climate and Environmental Sciences Division, BER

 

BER supports basic research and scientific user facilities to advance DOE missions in energy and environment. More about BER

Recent Highlights

May 10, 2019
Quantifying Decision Uncertainty in Water Management via a Coupled Agent-Based Model
Considering risk perception can improve the representation of human decision-making processes in age [more...]

May 09, 2019
Projecting Global Urban Area Growth Through 2100 Based on Historical Time Series Data and Future Scenarios
Study provides country-specific urban area growth models and the first dataset on country-level urba [more...]

May 05, 2019
Calibrating Building Energy Demand Models to Refine Long-Term Energy Planning
A new, flexible calibration approach improved model accuracy in capturing year-to-year changes in bu [more...]

May 03, 2019
Calibration and Uncertainty Analysis of Demeter for Better Downscaling of Global Land Use and Land Cover Projections
Researchers improved the Demeter model’s performance by calibrating key parameters and establi [more...]

Apr 22, 2019
Representation of U.S. Warm Temperature Extremes in Global Climate Model Ensembles
Representation of warm temperature events varies considerably among global climate models, which has [more...]

List all highlights (possible long download time)