At pH of ~3, we assume the tartaric acid buffer would form a strong H-bond with the surface-exposed deprotonated Glu250. To test the possibility of such case, a tartaric acid molecule was docked into the proximity of Glu250, based on which we carried out the classical MD and QM/MM MD simulations. Our QM/MM MD simulations indicated that the tartaric acid molecule could form a persistent and strong H-bond with Glu250, with an average O--H distance of 1.69 Å (Figure ). Similar to the case without tartaric acid, our QM/MM MD simulation also showed a fast ET from Trp171 to Cpd I, which yielded the Cpd II and Trp171 cation radical, when the tartaric acid was available. This could be confirmed by the spin density accumulation in Trp171 after the fast ET (see Figure ). In addition, QM/MM MD simulations show the ET process can be crossed back (Figure ) , suggesting that the first ET step with tartaric acid is almost thermally neutral, which is in line with the QM-calculated value of 0.63 kcal/mol for the reaction free energy (Figure ). However, further QM/MM MD simulation did not lead to a final PT from the Trp171 cation radical to Glu250, suggesting the presence of a strong H-bond with tartaric acid can significantly undermine the basicity of Glu250 for proton reception. This observation agrees with our QM calculations (Figure ), showing that this step is endoergic by 3.8 kcal/mol. Thus, our simulations suggest that the mechanism of the first ET step transpires via a pure ET mechanism in the presence of tartaric acid.