  Quantum Mechanics/Molecular Mechanics (QM/MM) simulations are a popular
approach to study various features of large systems. A common application of
QM/MM calculations is in the investigation of reaction mechanisms in
condensed-phase and biological systems. The combination of QM and MM methods to
represent a system gives rise to several challenges that need to be addressed.
The increase in computational speed has allowed the expanded use of more
complicated and accurate methods for both QM and MM simulations. Here, we
review some approaches that address several common challenges encountered in
QM/MM simulations with advanced polarizable potentials, from methods to account
for boundary across covalent bonds and long-range effects, to polarization and
advanced embedding potentials.
