Theory 39/Protein Folding
Aggregation Is a Patch Ratio
The claim
Aggregation propensity is set by the ratio of hydrophobic patch area to net charge rather than by hydrophobicity alone, so a strongly hydrophobic protein can stay soluble if it is charged enough.
01The mechanism
Aggregation requires patches to meet; charge provides electrostatic repulsion that keeps them apart, so the balance of the two sets the risk.
02Predictions
- P1Propensity should track the patch ratio.
- P2Hydrophobicity alone should mispredict.
03Refutation
Propensity tracking hydrophobicity would remove the charge term.