Ultrafast Quantum Mechanics/Molecular Mechanics Monte Carlo simulations using generalized multipole polarizabilities

► A very fast and accurate method is presented for QM/MM simulation of solutions. ► The quantum energy in the solvent electric field is determined from precalculated quantities. ► Precalculated generalized moments and polarizabilities allow fast quantum energy calculation. ► Our method is four orders of magnitude faster than the recalculation of the quantum energy. ► The method is virtually exact with polarizabilities included; without them, errors are ∼20 kJ/mol.