Despite several previous attempts to model the creation of G-T wobble mismatches, the presence and role of quantum effects in this reaction have not been addressed, with previously reported semi-classical models severely underestimating the experimental reaction rates. In the following, we introduce a first-principles based quantum dynamic approach for modelling proton tunnelling in a realistic cellular environment, which accounts for the noise and thermal fluctuations of the biological system. We then employ this method to calculate the G-T wobble mismatch reaction pathway to the Watson-Crick-like configuration and the double proton transfer scheme in the Watson-Crick-like configuration (see Fig. ).