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.a. 诸多参数对酸碱度（pH）均表现出极高敏感性，例如Gag-Pol自剪切[8,9]、PR（Protease）二聚化[14]以及异源分子剪切速率。目前病毒颗粒内部的酸碱度尚不明确，但可假定其接近PR发挥活性的最适pH（约5.5），因此我们优先选用在此pH条件下获得的参数估计值（若有相关数据）。 初始浓度基于文献[22]的数据计算得到，具体步骤如下：病毒半径r=63 nm=6.3×10⁻⁷ dm；Gag分子数量为2280；Gag-Pol分子数量为120（Gag总含量为2400）。病毒颗粒体积V=(4πr³)/3≈1.05×10⁻¹⁸ dm³。考虑到1摩尔包含6×10²³个分子，经计算可得：2280/(6×10²³)=3.8×10⁻²¹ mol，120/(6×10²³)=2×10⁻²² mol；进一步换算得到浓度分别为3.8×10⁻²¹ /1.05×10⁻¹⁸≈3.619×10⁻³ mol/dm³，以及2×10⁻²² /1.05×10⁻¹⁸=1.9047×10⁻⁴ mol/dm³。 b. 目前未获取到这两个剪切位点的直接实验估计值。我们采用其余经典剪切位点的KM（Michaelis constant，米氏常数）值中位数，并基于文献[18]提供的数据估算kcat（catalytic rate constant，催化速率常数），详细推导过程参见补充文本S1。 c. 对应文献[15]中报道的3个内部剪切位点里速率最快的一个。 d. 采用两个已报道值（1.3和0.7×10⁻³）的平均值。 e. 指中间形式（二聚体）：其N端已被释放，但至少一个单体的C端侧翼片段仍未被剪切。 f. 未获取到全长Gag-Pol及中间酶形式的实验估计值。参照成熟PR，通过分别将结合速率常数（association rate constant，kass）降低1个和2个数量级，以体现推测的催化效率下降。 g. 除全长Gag-Pol二聚体外，该类别还包含自剪切的首个中间产物：MA.INTdPR.INT。 表格缩写说明：本表格所用缩写的含义如下：kcat（催化速率常数，catalytic rate constant）、KM（米氏常数，Michaelis constant）、kass（结合速率常数，association rate constant）、kdiss（解离速率常数，dissociation rate constant）。