Fig. 5. Monte Carlo simulations of fibril formation via globular pre-fibrillar oligomers. (a) Reaction network; all fibrillar oligomers are included in the product node. The flux to fibrils is due to conformational conversion of pre-fibrillar to fibrillar oligomers. (b) Conversion rate constant vs. oligomer size j; this peaks at j = 6. (c) Size distribution of oligomers at steady state; this decreases with j apart from a j = 4–14 plateau. (d) The proportion of the total flux to fibrillar species going via each conversion reaction (given by the normalized product of (b) and (c)). (e) Pathway index p_i (equal in this case to the sensitivity index ξ) vs. pre-fibrillar oligomer size. An oligomer of size j carries all the flux for all conversion reactions for oligomers ≥j; therefore, ξ_j is given by summing (d) over all conversion reactions ≥j. Dashed lines illustrate the result of alternative investigator-defined cut-offs (the examples given are 5, 20 and 50%) for a binary on-/off-pathway definition.