Parameters used for the simulation of the modela.

aMany parameters are very sensitive to pH (for example Gag-Pol auto-cleavage [8], [9], PR dimerization [14] and also the rates of heteromolecular cleavage). The pH within virions is unclear; however, it may be assumed to be close to the optimum for PR activity (pH∼5.5), we have therefore selected parameter estimates obtained at this pH wherever available.Initial concentrations were calculated based on data from [22] as follows. Radius of the virus: r = 63 nm = 6.3×10−7 dm; number of Gag molecules: 2280; number of Gag-Pol molecules: 120 (total Gag content: 2400). The volume of a virion V = (4π(r3))/3≈1.05×10−18 dm3. Considering that 1 mol consists of 6×1023 molecules, (2280/(6×1023) = 3.8×10−21 mol and 120/(6×1023) = 2×10−22 mol, then 3.8×10−21/1.05×10−18≈3.619×10−3 mol/dm3 and 2×10−22/1.05×10−18 = 1.9047×10−4 mol/dm3.bNo direct estimates were available for these two cleavage sites. We used the median of the KM values estimated for the other canonical cleavage sites, and estimated kcat from data presented in [18] (see supplementary Text S1).cReflecting the fastest of three internal cleavage sites reported in [15].dThe mean of the two reported values (1.3 and 0.7×10−3) was used.eIntermediate forms (dimers) with liberated N-termini but C-terminal flanking fragments still uncleaved in at least one of the monomers.fNo empirical estimates were available for full length Gag-Pol and intermediate enzyme forms. Presumed decreased efficiency was implemented by decreasing the association rate with one and two orders of magnitude, respectively, compared with the mature PR.gIn addition to full-length Gag-Pol dimer, this category included the first intermediate product of auto-cleavage: MA.INTdPR.INT.Abbreviations in the table: kcat – catalytic rate constant; KM – Michaelis constant; kass – association rate constant; kdiss – dissociation rate constant.