CCL: QM/MM computational cost?

Greetings CCLers.  Can anyone point me to a reference discussing the computational cost of QM/MM simulations and how it scales with size of the components?  I have some experience with quantum chemistry simulations, as well as molecular dynamics simulations, but I'm new to QM/MM and am being asked as part of a proposal I'm writing to discuss the computational cost of the calculations I want to do.  Right now the plan is to solvate a simple 6 atom quantum mechanical system with approximately 1000 TIP4P water molecules.

Thanks in advance for any help you can provide.

J. Nathan Scott
Graduate Student
University of Pennsylvania
Biochemistry and Molecular Biophysics Graduate Group
Work Phone: +1.215.898.8783