The MOLPRO program package can be used in combination with other software to perform hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) calculations. Through the use of point charges, electrostatic embedding can be used for both energy and gradient runs. In particular, lattices of point charges can be included in an external file, gradients with respect to charge positions can be computed, as described in section 10.5. Gradients with respect to QM nuclear positions can be computed (and include the effect of the MM charges) as usual using the FORCE command (section 45).
Although MOLPRO itself does not offer any interface to force field programs, the coupling is supplied by other commercial and non-commercial software. The following is a list of QM/MM software which allow the use of MOLPRO.