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PPT : Putting Engineering back into Protein Engineering

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Protein Engineering Current Paradigms
* Mechanism-based
o (Rational) detailed structural analysis
* Empiricism-based
o (Non-rational ) libraries based

Mechanism-Based Protein Engineering
Based on thermodynamic principles
* Calculations are approximate
o calculation cost
o structures are really not rigid (MDS)
* Calculations are primarily able to predict binding
o catalysis is a special case of binding to a transition state
* Changes in amino acids are designed based on these principles
o very small numbers (<5) of new proteins are synthesized and tested

Empiricism-Based Protein Engineering
* Uses similar principles to evolution
o make many variants
o screen to find those with the best properties
* No mechanistic understanding needed
* Produces large numbers of variants (>1,000) which are very difficult / expensive to screen for practically relevant properties

Proteins related to wild type
Simulated cross over

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PPT : Putting Engineering back into Protein Engineering Category : Protein
Source : www.soe.ucsc.edu
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