Optimal scanning of all single-point mutants of a protein

J Comput Biol. 2013 Dec;20(12):990-7. doi: 10.1089/cmb.2013.0026. Epub 2013 Jul 16.

Abstract

In protein engineering, useful information may be gained from systematically generating and screening all single-point mutants of a given protein. We model and analyze an iterative two-stage procedure to generate all these mutants. At each position, L variants are generated in the first stage via saturation mutagenesis and are sequenced. In the second stage, the missing variants (out of the 19 possible single-point substitutions) are produced via site-directed mutagenesis. We study the economic tradeoff associated with varying L, and derive its optimal value given the experimental parameters.

MeSH terms

  • Algorithms*
  • Animals
  • Humans
  • Mutagenesis, Site-Directed
  • Mutation / genetics*
  • Protein Engineering*
  • Proteins / genetics*

Substances

  • Proteins