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Protein design by directed evolution.

Christian Jäckel1, Peter Kast, Donald Hilvert

  • 1Laboratory of Organic Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland. jaeckel@org.chem.ethz.ch

Annual Review of Biophysics
|June 25, 2008
PubMed
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Protein design mimics evolution to create novel proteins rapidly. Combining lab experiments and computational methods accelerates the discovery of tailored protein catalysts and receptors for new applications.

Area of Science:

  • Biochemistry and Molecular Biology
  • Protein Engineering
  • Synthetic Biology

Background:

  • Nature evolved polypeptides over billions of years.
  • Protein design by evolutionary mimicry is advancing rapidly.
  • Laboratory imitation of evolutionary cycles (mutation, selection, amplification) is feasible.

Purpose of the Study:

  • To address the challenge of the vast polypeptide sequence space in protein design.
  • To highlight the importance of intelligently designed libraries and advanced search techniques.
  • To explore the potential of combined experimental and computational methods for protein engineering.

Main Methods:

  • Mimicking evolutionary cycles (mutation, selection, amplification) in the laboratory.
  • Utilizing existing proteins or de novo sequences as starting templates.

Related Experiment Videos

  • Employing intelligently designed libraries and improved search techniques.
  • Integrating experimental and computational approaches.

    • Main Results:

    • Accelerated progress in protein design through evolutionary mimicry.
    • Identification of challenges posed by the immense number of possible polypeptide sequences.
    • Demonstration of the promise of combined methods for creating novel protein functions.

    Conclusions:

    • Combining experimental and computational methods is crucial for future advances in protein design.
    • Tailored protein receptors and catalysts can be created for applications beyond natural scope.
    • Intelligent library design and search strategies are key to overcoming sequence space limitations.