The performance of different link atom based frontier treatments in QM/MM simulations was evaluated critically with SCC-DFTB as the QM method. In addition to the analysis of gas-phase molecules as in previous studies, an important element of the present work is that chemical reactions in realistic enzyme systems were also examined. The schemes tested include all options available in the program CHARMM for SCC-DFTB/MM simulation, which treat electrostatic interactions due to the MM atoms close to the QM/MM boundary in different ways. In addition, a new approach, the divided frontier charge (DIV), has been implemented in which the partial charge associated with the frontier MM atom ("link host") is evenly distributed to the other MM atoms in the same group. The performance of these schemes was evaluated based on properties including proton affinities, deprotonation energies, dipole moments, and energetics of proton transfer reactions. Similar to previous work, it was found that calculated proton affinities and deprotonation energies of alcohols, carbonic acids, amino acids, and model DNA bases are very sensitive to the link atom scheme; the commonly used single link atom approach often gives error on the order of 15 to 20 kcal/mol. Other schemes give better and, on average, mutually comparable results. For proton transfer reactions, encouragingly, both activation barriers and reaction energies are fairly insensitive (within a typical range of 2-4 kcal/mol) to the link atom scheme due to error cancellation, and this was observed for both gas-phase and enzyme systems. Therefore, the effect of using different link atom schemes in QM[MM simulations is rather small for chemical reactions that conserve the total charge. Although the current study used an approximate DFT method as the QM level, the observed trends are expected to be applicable to QM/MM methods with use of other QM approaches. This observation does not mean to encourage QM/MM simulations without careful benchmark in the study of specific systems, rather it emphasizes that other technical details, such as the treatment of long-range electrostatics, tend to play a more important role and need to be handled carefully.