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Protein engineering reflects the active design of protein properties by changing its amino acid sequence. This goal can be approached via rational design, combinatorial design, or a combination, termed data-driven protein engineering. Among the two principal strategies of tackling the huge size of protein sequence space, this chapter focuses on restricting the sequence space rather than on increasing the library size. Efficient variant generation can be achieved both by picking a limited number of residues to be mutated as well as by restricting the set of amino acid residues to code for.

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