Polarizable Density Embedding for Large Biomolecular Systems

We present an efficient and robust fragment-based quantum–classical embedding model capable of accurately capturing effects from complex environments such as proteins and nucleic acids. This is realized by combining the molecular fractionation with conjugate caps (MFCC) procedure with the polarizable density embedding (PDE) model at the level of Fock matrix construction. Thereby we avoid complications associated with the application of the fragmentation procedure on environment quantities such as density matrices and molecular orbital energies. We analyze the performance of the resulting model in terms of the reproduction of electrostatic potentials of an insulin monomer protein and further in the context of solving problems related to electron spill-out. Finally, we showcase the model for the calculation of one- and two-photon properties of the Nile Red molecule in protein environments. Based on our analyses, we find that the combination of the MFCC approach with the PDE model is an efficient yet accurate approach for calculating molecular properties of molecules embedded in structured biomolecular environments.