Pareto Optimization of Combinatorial Mutagenesis Libraries.

ABSTRACT: In order to increase the hit rate of discovering diverse, beneficial protein variants via high-throughput screening, we have developed a computational method to optimize combinatorial mutagenesis libraries for overall enrichment in two distinct properties of interest. Given scoring functions for evaluating individual variants, POCoM (Pareto Optimal Combinatorial Mutagenesis) scores entire libraries in terms of averages over their constituent members, and designs optimal libraries as sets of mutations whose combinations make the best trade-offs between average scores. This represents the first general-purpose method to directly design combinatorial libraries for multiple objectives characterizing their constituent members. Despite being rigorous in mapping out the Pareto frontier, it is als

SUBMITTER: Verma D 

PROVIDER: S-EPMC8262366 | biostudies-literature | 2019 Jul-Aug

REPOSITORIES: biostudies-literature