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Protein design has traditionally relied on an expert's ability to assimilate a myriad of factors that together influence the stability and uniqueness of a protein structure. As many of these forces are subtle and their simultaneous optimization is a problem of great complexity, sophisticated sequence prediction algorithms have been developed to aid in the design of novel proteins by providing quantitative analysis of the sequence-structure relationship. This review discusses some of the majordoi:10.1039/b313669h fatcat:4v7kua5e75hu3ke2ogp5zka4ua