Modeling and optimization of DNA recombination

This paper discusses predictive models for quantifying the outcome of DNA r ecombination employed in directed evolution experiments for the generation of novel enzymes. Specifically, predictive models are outlined for (i) trac king the DNA fragment size distribution after random fragmentation and subs equent assembly into genes of full length and (ii) estimating the fraction of the assembled full length sequences matching a given nucleotide target. Based on these quantitative models, optimization formulations are construct ed which are aimed at identifying the optimal recombinatory length and pare nt sequences for maximizing the assembly of a sought after sequence target. Computational results show that the recombination outcome is a 'complex' f unction of the recombinatory length and recombined sequences and illustrate the magnitude of improvements that can be realized. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.