Part of our research concerns the accurate description of electrostatic potentials in proteins and enzymes. The goal is to incorporate polarization effects in describing molecular interactions, providing first principles detail, and constructing efficient algorithms that scale linearly or quadratically with the size of the macromolecular system. We have developed the Moving-Domain QM/MM method to treat polarization effects in proteins. In addition, an open problem in modeling chemical events in QM/MM methods is how to incorporate solvent effects via continuum dielectric models. Considering that many chemical reactions of biological relevance take place near a liquid solution phase, an accurate theoretical treatment of such processes must incorporate a realistic description of environmental effects. We have been working on a scalable method based on a charge density fragmentation of a conductor-like screening model (DDF-COSMO), which can be incorporated into QM/MM and MOD-QM/MM.
