Protein Redesign Summary

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Protein Redesign - Summary

• GoalTo engineer improved or new proteins
• Two typesA. Rational RedesignB. Semi-rational
  (combinatorial) Redesign
• Considerations1. Protein architecture/topology2
  . Sequence to structure/function rules3.
  Expression/solubility/stability

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De Novo Protein Design

• The basics

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What do we need to know to design new protein
structures?

• Limits on protein architecture topology
• Rules that link sequence and structure

These are harder than than they first appear so
the trick is to choose simple target structures
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Choose the sensible target forde novo design
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Why bother with de novo design?

• To make wildly new protein structures
  functions
• It is the acid test of our understanding of
  protein structure and folding

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Considerations in de novo design

• Protein architecture/topology
• Sequence to structure/function rules
• Expression/solubility/stability
• Specificity Negative design

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Compare Contrast 2 Systems

• Evolution of a 4-helix-bundle designDeGrado et
  al over the past 2 decades
• Rational design of coiled-coil proteinsKim et al
  over the past decade