Using Quantitative Measures of Natural Selection for Rational Protein Engineering

This invention utilizes quantitative metrics of molecular evolution to define effectively mutable protein space that can be targeted in rational protein engineering enterprises focused on improving protein function and/or altered relatedness to proteins protected by pre-existing competing patents. The core technology is to use quantitative metrics of natural selection to define "effectively mutable protein space" and thereby greatly improve the efficiency of targeted protein engineering enterprises by greatly reducing the sites for directed mutagenesis. This enabling technology is suitable for synthetic biology applications that rationally redesign or engineer existing proteins into modified versions that now recognize new substrates and/or produce new reaction products. This technology is also suitable for re-engineering proteins to retain similar functionality but demonstrate improved physio-chemical properties. Another implementation of this invention is to identify amino acid positions that can be altered without significantly altering protein function, and result in significantly altered amino acid composition in protein sequence alignments that will circumvent competing pre-existing patents that have a defined threshold of protein relatedness.
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Mike Miller
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John Jelesko