Our QM/MM MD simulations showed that the strong Hbond between Glu250 and the tartaric acid could significantly undermine the H-bond interaction between Glu250 and Trp171. In the presence of the tartaric acid, the H-bond distance between Glu250 and Trp171 increased by 0.9 Å (Figure ). This would shift the Trp171 towards its protonated state, which has a significantly higher reduction potential than its deprotonated form, hence enhancing the oxidizing power of the Trp171 radical. Indeed, such a hypothesis is well supported by our QM model calculations (see Figure ). Our QM calculations showed that the electron affinity of the Trp171 cation radical increases along with the elongation of H-bond length between Glu250 and Trp171. In addition, the electron affinity of the Trp171 cation radical decreases along with the elongation of the Hbond between Glu250 and the tartaric acid (see Figure ). Hence, the presence of a strong H-bond between Glu250 and the tartaric acid could significantly weaken the H-bond between Glu250 and Trp171, which could elevate the electron affinity of the Trp171 cation radical therefore facilitate the ET from the lignin substrate to the Trp171 cation radical. In general, through donating a H-bond to Glu250, the acid buffer can efficiently enhance the favoritism of the second ET step hence facilitate the enzyme catalysis. 3. Revised mechanism. In Scheme 2, we proposed the revised mechanisms of long-range ET occurring in lignin peroxidase without with diprotic acid based on the QM/MM MD simulations. In the absence of the tartaric acid, our simulations showed a ETPT mechanism for the first ET step. The PT step is fast enough as observed by our QM/MM simulation, suggesting the ET step is the rate-determining step in this ETPT mechanism. However, our results indicated a concerted PCET mechanism for the second ET step without tartaric acid. In comparison, in the presence of the tartaric acid, our simulations suggested for an ET mechanism for both the first and second ET steps.