Figure 4: Rational design of β2m mutants.

(A) Aggregation-prone residues (intrinsic score > 1) for which the protective effect of the W60G mutation is the highest, defined as those residues with the largest change in the structurally-corrected score between the wild-type (red) and W60G (black) β 2m. (B) Predicted aggregation propensity scores calculated using CamSol for all possible amino acid substitutions at the sites shown in panel A in the wild type (left box-plot in red) and in the W60G variant (right box-plot in black). The red and black dashed lines correspond to the aggregation propensity score of the WT and the W60G variant, respectively. Aggregation-protective and aggregation-promoting mutations selected for experimental validation are flagged. V85E and N83V mutations have been chosen as those with the largest predicted effect, while Y63W was chosen as a weakly aggregation promoting mutation. In each box the horizontal line denotes the median of the distribution; whiskers extend from the 5th to the 95th percentile of the distribution and boxes from the lower to the upper quartile.