In silico nucleic acid recombination methods, related integrated systems utilizing genetic operators and libraries made by in silico shuffling methods are provided. One disclosed method involves identifying and producing a polypeptide. The method may involve (a) receiving data identifying sequences of two or more parental polypeptides or parental nucleic acids that encode the polypeptides; (b) selecting one or more cross-over sites on the sequences thereby defining one or more recombinant polypeptides or recombinant nucleic acids; (c) selecting at least one of the recombinant polypeptides or recombinant nucleic acids; (d) recombining one or more oligonucleotides, at least one of which has a sequence matching some or all of that of the recombinant polypeptides or recombinant nucleic acids selected in (c); (e) selecting at least some of the recombined oligonucleotides produced in (d); and (f) producing a polypeptide encoded by the selected nucleic acid.