Reliable ligand discrimination in stochastic multistep kinetic proofreading: First passage time vs. product counting strategies
Fig 1
Schematic of the KPR process and different strategies of interpreting the output.
(A) The complex of enzyme and substrate ES alone cannot produce the final product P. It has to undergo a number of proofreading steps, represented here by phosphorylation (Pi), before the activated state E*S can produce the final product. (B) The FPT-based discrimination strategy, simply reaching the activated state E*S is interpreted as the output. Xa(t) = 0 if the system has not reached the activated state by time t, and Xa(t) = 1 otherwise. At t = 0, the reaction starts with the enzyme in the free state E. The dashed vertical line represents the termination of entire process, e.g., the time T at which the T cell and antigen presenting cell (APC) separate. Xa(t) = 1 for some t < T is interpreted as a positive response. (C) The product-based discrimination strategy. In this strategy, the number of product molecules P(T) produced within a given time T is interpreted as the output. Due to the intrinsic noise, the number of product molecules is a random variable and their distribution is shown for correct and incorrect ligands.