Extended to the aggregation reaction, the Φ-value is defined as ∆∆G ‡-U /∆∆G A-U . A Φ-value close to 1 indicates that the mutated residue is likely to have formed most of its fibril contacts in the TS, while a Φ-value close to 0 indicates that the mutated residue is likely to have formed no contacts in the TS (See Fig 1).