Two antisymmetric combinations of distances were selected as reaction coordinates to describe the transfer of both hydrogen atoms: rC2H-rOH (proton abstraction) and rC1H-rNH (hydride transfer). One-dimensional potential energy scans were performed to generate the initial structures for QM/MM MD simulations. The reaction was studied with the umbrella sampling method , at each window of simulation a parabolic penalty potential was added with a force constant of 2500 kJ/Å 2 mol. One QM/MM MD simulation consisted of 5 ps of system relaxation, and then 20 ps of simulation, results of which were used for further analysis. The weighted histogram analysis method was used to combine the QM/MM MD results into a distribution function. QM/MM MD simulations were run at the AM1/AMBER level of theory .