Two-pathway four-state kinetic model of thioredoxin-catalyzed reduction of single forced disulfide bonds.

Recent single-molecule experiments found that the thioredoxin-catalyzed reduction of individual disulfide bonds placed under a stretching mechanical force has distinct characteristics: the reduction rate of human thioredoxin monotonically decreases with the force, while the rate of E. coli thioredoxin first decreases and then increases as the force goes beyond a certain threshold. In this work, we present a force-dependent two-pathway four-state model to uniformly quantify these intriguing observations. Although our model is indistinguishable from the previous two-pathway three-state model in predicting the mean reduction rate, the distributions of dwell times of the two models are significantly distinctive. The very recent experiment favors our model.