Noncontiguous SCHEMA protein recombination.

SCHEMA is a method of designing protein recombination libraries that contain a large fraction of functional proteins with a high degree of mutational diversity. In the previous chapter, we illustrated the method for designing libraries by swapping contiguous sequence elements. Here, we introduce the NCR ("noncontiguous recombination") algorithm to identify optimal designs for swapping elements that are contiguous in the 3-D structure but not necessarily in the primary sequence. To exemplify the method, NCR is used to recombine three fungal cellobiohydrolases (CBH1s) to produce a library containing more than 500,000 novel chimeric sequences.