| 摘要 |
<p>A method of predicting the effect of an amino acid modification the rate of aggregation of a second polypeptide in comparison to the rate of aggregation of a reference polypeptide, wherein the second polypeptide comprises one of more amino acid modification when compared to the reference polypeptide, comprising: a) determining a difference in hydrophobicity between the reference and second polypeptide; b) determining a difference in secondary structure between the two polypeptides; c) determining a difference in charge between the polypeptides; and forming a weighted combination of said differences in order to determine the relative rate of aggregation. In one embodiment, the prediction of effect of the amino acid substitution can be expressed by calculating the difference in hydrophobicity ( W Hydr), the difference in b-sheet propensity ( WW Gcoil- a + WW G b -coil), the difference in charge ( W Charge), and calculating [x* W Hydr] + [y*( WW Gcoil- a + WW G b -coil)] - [z* W Charge], wherein X, y, and z are scaling factors. Methods for making reduced aggregation peptides are also disclosed. Also provided are computer programs and computer systems for predicting the rates of aggregation.</p> |
