Figure 5. Rate of EF-Tu dissociation influences the proofreading factor P_f.

(a) P_f is shown as a function of for the induced fit mechanism of proofreading (Fig. 4c). For this calculation, accommodation of cognate tRNA is modelled as being 50-fold faster than near-cognate: . Only =10 is shown since P_f is only sensitive to this ratio when it is <1. (b) For the EA-destabilized mode of proofreading (Fig. 4d), P_f depends on the relative rates of EF-Tu dissociation and 3′-CCA accommodation . Each curve is labelled by the value of the relative rate of 3′-CCA accommodation (). A representative value of ΔΔF_NC=8 k_BT was used to demonstrate the overall behaviour of P_f. In contrast to the induced fit description, proofreading through EA destabilization depends on the value of k_CCA. This is because, when tRNA is in the EA basin, the reverse step for near-cognate tRNA, with a rate of , will be competitive with forward accommodation (rate of k_CCA). In contrast, the reverse barrier is large for all molecules in the induced-fit framework. Common to both descriptions is that fidelity increases monotonically with the rate of EF-Tu dissociation k_−Tu. Solid (dashed) lines distinguish between regions where efficiency is greater (less) than 0.9. As the rate of EF-Tu dissociation increases, the efficiency decreases. This suggests that EF-Tu dissociation should be sufficiently slow, such that it may accelerate elbow accommodation (increase efficiency), yet fast enough to allow for rejection (increase selectivity).