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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
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Computational protein design with backbone plasticity.

James T MacDonald1,2, Paul S Freemont1,2

  • 1Centre for Synthetic Biology and Innovation, South Kensington Campus, London SW7 2AZ, U.K.

Biochemical Society Transactions
|December 3, 2016
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Summary
This summary is machine-generated.

Computational protein design advances artificial enzymes. Incorporating backbone flexibility, though challenging, overcomes limitations of natural scaffolds for novel protein engineering.

Keywords:
computational protein designconformational samplingflexible backbone design

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Area of Science:

  • Biochemistry
  • Computational Biology
  • Protein Engineering

Background:

  • Computational protein design has advanced significantly, enabling the creation of artificial proteins with novel functions.
  • Artificial enzyme design, a key success, often relies on natural protein scaffolds for novel functionality.
  • Integrating backbone flexibility into computational design presents challenges due to increased search space but offers greater design freedom.

Purpose of the Study:

  • To review the principles of computational protein design methods.
  • To discuss recent advancements in incorporating backbone flexibility into protein design.
  • To highlight the potential of backbone plasticity in overcoming limitations of natural protein scaffolds.

Main Methods:

  • Review of computational algorithms for protein design.
  • Analysis of strategies for incorporating backbone flexibility.
  • Discussion of successes and challenges in de novo enzyme design.

Main Results:

  • Sophisticated computational algorithms have led to remarkable successes in artificial protein design.
  • The de novo design of artificial enzymes represents a significant achievement.
  • Reusing natural protein scaffolds is a common approach, but backbone flexibility offers a path beyond these limitations.

Conclusions:

  • Computational protein design is a rapidly evolving field with significant potential.
  • Addressing backbone flexibility is crucial for advancing the design of artificial proteins beyond natural scaffolds.
  • Future efforts should focus on computationally tractable methods to incorporate backbone plasticity for broader applications.