Abstract: A method and data processing system for identifying mutations or insertions that alter a property such as the solubility or aggregation propensity of an input polypeptide chain. The method comprises inputting a sequence of amino acids and a structure for said sequence for said target polypeptide chain; calculating a structurally corrected solubility or aggregation propensity profile for said target polypeptide chain; selecting, using said calculated profile, regions within said target polypeptide chain; identifying at least one position within each selected region suitable for mutations or insertions; generating a plurality of mutated sequences by mutations or insertions at least one identified position; and predicting a value of the solubility or aggregation propensity for each of the plurality of mutated sequences whereby any alteration to the solubility or aggregation propensity of the input polypeptide chain is identified.