We have studied a protein misfolding reaction that is directly relevant for most diseaserelated amyloids with no significant residual structure in the monomeric precursor, such as the Aβ peptide, tau and α-synuclein. Another important scenario is presented by protein systems that are predominantly folded under the conditions of the misfolding reaction (e.g. human lysozyme ). In such cases the rate limiting barrier may be either monomer unfolding or binding of the unfolded monomer to the fibril end . The exact nature of the rate-limiting step in such cases remains mostly unexplored and combinations of classical Φ-value analysis and the approach outlined here may illuminate these processes.