Optimal protein library design using recombination or point mutations based on sequence-based scoring functions

Robert J. Pantazes, Manish C. Saraf, Costas D. Maranas

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

In this paper, we introduce and test two new sequence-based protein scoring systems (i.e. S1, S2) for assessing the likelihood that a given protein hybrid will be functional. By binning together amino acids with similar properties (i.e. volume, hydrophobicity and charge) the scoring systems S1 and S2 allow for the quantification of the severity of mismatched interactions in the hybrids. The S2 scoring system is found to be able to significantly functionally enrich a cytochrome P450 library over other scoring methods. Given this scoring base, we subsequently constructed two separate optimization formulations (i.e. OPTCOMB and OPTOLIGO) for optimally designing protein combinatorial libraries involving recombination or mutations, respectively. Notably, two separate versions of OPTCOMB are generated (i.e. model M1, M2) with the latter allowing for position-dependent parental fragment skipping. Computational benchmarking results demonstrate the efficacy of models OPTCOMB and OPTOLIGO to generate high scoring libraries of a prespecified size.

Original languageEnglish (US)
Pages (from-to)361-373
Number of pages13
JournalProtein Engineering, Design and Selection
Volume20
Issue number8
DOIs
StatePublished - Aug 2007

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Molecular Biology

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