Ribosome utilizes the minimum free energy changes to achieve the highest decoding rate and fidelity

The performance of ribosome translation can be characterized by two factors, the translation rate and fidelity. Here, we provide analytical studies of the effect of the near-cognate tRNAs on the two factors. It is shown that the increase of the concentration of the near-cognate tRNAs relative to that of the cognate tRNA has negative effects on the ribosome translation by reducing both the translation rate and the translation fidelity. The effect of the near-cognate ternary complexes on the translation rate results mainly from the initial selection phase, whereas the proofreading phase has a minor effect. By contrast, the effect of the near-cognate ternary complexes on the fidelity results almost equally from the two phases. By using two successive phases, the initial selection and the proofreading, the ribosome can achieve higher translation fidelity than the product of the fidelity when only the initial selection is included and when only the proofreading is included, especially at the large ratio of the concentration of the near-cognate tRNAs compared to that of the cognate tRNA. Moreover, we study the changes of the free energy landscape in the tRNA decoding step. It is found that the rate constants of the tRNA decoding step measured experimentally give the minimum energy changes for the ribosomal complex to attain the optimal performance with both the highest decoding rate and fidelity and/or with the maximum value of the decoding fitness function. This suggests that the ribosome has evolved to utilize the minimum free energy changes gained from the conformational changes of the ribosome, EF-Tu, and tRNA to achieve the optimal performance in the tRNA decoding.