RATIONAL METHOD FOR SOLUBILISING PROTEINS

摘要

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. Predicting a value for solubility or aggregation propensity comprises: inputting each of the plurality of mutated sequences as an input polypeptide chain into a data processing system comprising a first trained neural network having a first function mapping an input to a first output value and a second trained neural network having a second function mapping an input to a second output value; generating a first output value of said solubility or aggregation propensity for each said input polypeptide chain using said first trained neural network; generating a second output value of said solubility or aggregation propensity for each said input polypeptide chain using said second trained neural network; and combining the first and second output values to determine a combined output value for the solubility or aggregation propensity.