PEDS Advance Access published online on August 8, 2007
Protein Engineering Design and Selection, doi:10.1093/protein/gzm030
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Optimal protein library design using recombination or point mutations based on sequence-based scoring functions
Department of Chemical Engineering, The Pennsylvannia State University, University Park, PA 16802, USA
2 To whom correspondence should be addressed. E-mail: costas{at}psu.edu
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.
Keywords: hybrid scoring method/protein engineering/protein library optimization
Received February 8, 2007; revised May 25, 2007; accepted May 25, 2007.