< Back to Article

Reliable ligand discrimination in stochastic multistep kinetic proofreading: First passage time vs. product counting strategies

Fig 2

Reaction schemes of different descriptions of the simple kinetic proofreading process.

(A) The conventional description of KPR explicitly incorporating multiple proofreading steps. (B) A reduced representation of KPR in which multiple driven steps are lumped in a single proofreading step. Additionally, the state E*S can be taken to be a final “product” state E + P, in which case, there is no disassembly (marked by dashed lines) and . However, one may be interested in products P that are constitutively produced (at rate k_p) by the E*S state (gray). This latter scenario can describe, e.g., TCR-mediated T cell activation. (C) For comparison, we show the classical Michaelis-Menten reaction scheme in which the “product” state E + P can be identified as an activated complex E*S. The Michaelis-Menten kinetics implicitly assumes values of τ are exponentially distributed. An internal proofreading process leads to a nonexponentially distributed τ and equivalence to the scheme in (B) and describes the FPT-based DNA replication setting (without any additional constitutive product formation). In our setting, substrate concentrations are held fixed, and k₁ will be defined as a first-order reaction rate with physical units of 1/time.

doi: https://doi.org/10.1371/journal.pcbi.1012183.g002